L-ergothioneine naturally occurs in living organisms
L-ergothioneine is incorporated into tissues via a specific transporter
L-ergothioneine has a slow turnover
In search for the physiological role of L-ergothioneine
Viewpoint and perspectives

 

L-ergothioneine naturally occurs in living organisms

 

Chemical structure of L-ergothioneine

 

L-Ergothioneine is a natural and water-soluble compound which has been first isolated in rye ergot (Claviceps purpurea) in 1909 by the French pharmacist Charles Tanret [1].

To date, the only organisms known to be able to synthesize L-ergothioneine are bacteria, more specifically mycobacteria [2] and cyanobacteria [3], and fungi of the phyla AscomycotaZygomycota and Basidiomycota, which include lower fungi (molds) and higher edible fungi [4-9].

The biosynthesis of L-ergothioneine has been studied in Neurospora crassa [10-12] and mycobacteria [13]. In the first stage, L-histidine is methylated threefold by one specific N-methyltransferase to yield the betaine derivative L-hercynine, with S-adenosyl-methionine as the methylating agent. Sulfur is then added to L-hercynine in an oxidation reaction catalyzed by an iron-containing enzyme. In N. crassa and mycobateria, the reaction uses cysteine or γ-glutamylcysteine, respectively, as the sulfur-donating substrate. Both pathways pass through the formation of hercynyl-cysteine sulfoxide, which is cleaved to yield L-ergothioneine and pyruvate by a β-lyase, in the presence of pyridoxal phosphate.

L-Ergothioneine is found throughout the living world from plants to man, including in particular the well-known horseshoe crab (Limulus polyphemus), one of the oldest living animal species on Earth [14]. However, these organisms are unable to synthesize L-ergothioneine. Plants absorb L-ergothioneine via symbiotic associations between their roots and soil fungi [15,16]. Animals and humans only absorb L-ergothioneine via their respective food chains [3,5,17,18]. In animals, intestinal microbiota has been shown not to contribute to L-ergothioneine occurence in the body [19,20].

The determination of the L-ergothioneine content in common foods shows that edible mushrooms, black and red beans, oat bran, garlic and some meat products (liver and kidney) are the main dietary sources of this compound for man [21,22].

L-Ergothioneine has been identified or assayed in plant tissues [21,23,24] and animal tissues/fluids [14,25-46], including human ones [18,25,27,42,44,47-51].

For a given animal tissue or fluid, high variations are observed in L-ergothioneine concentration, which may of course reflect dietary variations but also the lack of specificity and sensitivity of earlier analysis methods. This highlights the need to verify older data using more recent analytical techniques such as liquid chromatography coupled to mass spectrometry [52].

L-Ergothioneine is distributed in most tissues, but unevenly, as shown in the mouse: liver > kidney ≃ heart > skin ≃ lung ≃ spleen ≃ small intestine ≃ blood (erythrocytes) > pancreas ≃ testis ≃ muscle ≃ large intestine ≃ brain [42]. Cross-species analysis of its content in organs also reveals differences across species [5,44].

Most often found in the sub-millimolar range, L-ergothioneine may reach millimolar concentrations in some tissues or fluids, for example the lens in man [48], various ocular tissues in cows and pigs [39], and seminal plasma in boars [44].

At subcellular level, it has been shown that L-ergothioneine is mainly distributed in the cytoplasm [28,32]. Use of tritiated L-ergothioneine enabled demonstration that it is also distributed, to a lesser extent, in membranes, mitochondria, nuclei and microsomes [32].

 

L-ergothioneine is incorporated into tissues via a specific transporter

About a century after the identification of L-ergothioneine, the discovery that it is the physiological substrate of the OCTN1 transporter [53] has boosted the knowledge of this unique natural compound. Earlier characterized in humans and described as a multispecific organic cation transporter [54,55], OCTN1 (also known as SLC22A4) was shown to have a high affinity for L-ergothioneine (Km=21μM) and to be specific for this substrate, whose transport is also sodium dependent (co-transport) [53,56]. ETT, for ergothioneine transporter, was thus proposed as a new name for OCTN1 [53].

In humans, the expression of OCTN1/ETT has been shown in numerous organs, with the highest level in bone marrow, small intestine, trachea, fetal liver, kidney, cerebellum and spinal cord [53,56]. In hematopoietic tissues, OCTN1/ETT is strongly expressed in the erythroid lineage, from the CD71+ (transferrin receptor) progenitor cells until mature erythrocytes [53,57]. In peripheral blood mononuclear cells, OCTN1/ETT is predominantly expressed in CD14+ and is absent in lymphocytes [53,58]. Taken together, these results show that OCTN1/ETT is associated with myeloid cells.

The expression of OCTN1/ETT has been evidenced on the cytoplasmic membrane of various cell types, such as Sertoli cells [59], endothelial cells [60,61], dermal fibroblasts [62,63], epidermal keratinocytes [63], brain neurons [45], neural progenitor cells [64], and epithelial cells, mainly apically in the latter, as evidenced in renal [65], pulmonary [66,67], ocular [68], small intestinal [69] and nasal [66,70] epithelial cells. In basal epidermal keratinocytes [63] and most probably in glandular cells of seminal vesicles [44], the expression of OCTN1/ETT is basolateral.

OCTN1/ETT expression has also been evidenced at mitochondrial level [71], but this result has been questioned [72].

Metabolomic analysis in OCTN1/ETT gene knockout mice has shown an almost complete disappearance of L-ergothioneine in the tissues of these mice [42]. This has also been shown in a more in-depth study of the various regions of the brain in the knockout mice [45] and in the OCTN1/ETT knockout zebra fish [73,74]. These studies confirm the key role of the OCTN1/ETT transporter in the tissue absorption of L-ergothioneine. Consistently, the tissue distribution of L-ergothioneine matches the OCTN1/ETT expression pattern and OCTN1/ETT mRNA expression is correlated to L-ergothioneine content [44,45].

OCTN1/ETT expression is up-regulated by pro-inflammatory cytokines (TNF-α, IL-1β) via activation of the transcription factor NF-κB [75,76], and is also under the control of the transcription factors Sp1 and RUNX1 [75].

OCTN1/ETT-gene variants have been associated with chronic inflammatory diseases in specific populations, e.g. the slc2F2 variant with rheumatoid arthritis [58,77] and the L503F variant with Crohn's disease [78,79], the latter being in particular associated with a slightly more efficient L-ergothioneine transport [80]. The involvement of these variants as causal genes for these diseases has not been demonstrated and is even questioned for the L503F variant [81]. Indeed, it has been suggested that the increase of L503F variant frequency is the result of genetic hitchhiking [82]. Interestingly, the authors of this study suggest that it would also be an adaptation to low dietary levels of L-ergothioneine among early Neolithic farmers in the Fertile Crescent [82]. Furthermore, a recently published study provides new insights supporting a beneficial effect of OCTN1/ETT on intestinal inflammation by mediating uptake of L-ergothioneine [76].

Finally, it is interesting to highlight that OCTN1/ETT knockdown studies support a role of this transporter and L-ergothioneine in cell proliferation and differentiation, as shown in erythroid cells [83] and neuronal cells [45,64].

 

L-ergothioneine has a slow tissue turnover

The kinetics of incorporation and tissue elimination of L-ergothioneine were studied in rodents, following oral absorption of L-ergothioneine [42,84-86] or after intraperitoneal or intravenous injection [35]. These studies show that L-ergothioneine has a slow turnover. It accumulates gradually and at different speeds in the organs and in blood, and it is also strongly retained in tissues.

A relatively early study in rats showed the effect of age and gender on the blood concentration of L-ergothioneine [85]. In that study, the authors show that, in rats maintained on a normal diet, the blood concentration of L-ergothioneine doubles during the first 3 months of life for both sexes. But while this concentration is stabilized up to 18 months (end of study) in the female, it reaches a plateau at a value twice as high in male rats. These authors have also shown that testosterone may be the cause of this increased accumulation in the male. No other study of gender effect on tissue concentration of L-ergothioneine has been reported to date.

The effect of age on erythrocyte concentration of L-ergothioneine was also identified in a population of men with an increase in concentration between the age of 1 and 10 years, which peaks at about 18 and decreases until about 50, when it stabilizes [49].

In rats, L-ergothioneine has been shown to pass from the mother to the neonate or pup during weaning via maternal milk [87], which is consistent with the evidencing of the OCTN1/ETT expression in the mammary epithelium [88,89].

In the current state of knowledge, no metabolite of L-ergothioneine has been identified so far in man or animals.

 

In search for the physiological role of L-ergothioneine 

The following intrinsic properties of L-ergothioneine have been shown in vitro:

  • Sequestering, reducing or disactivating highly oxidizing chemical entities: hypochlorous acid [90], peroxynitrite anion [91], peroxyl radicals [92], ferrylmyoglobin [93], singlet oxygen [94,95], and photosensitizer in the excitated state [96].
  • Chelating metal cations (copper, mercury, cadmium, zinc) [97-99] and, in particular, preventing the pro-oxidative effects of copper [100-102].

In a biological context, numerous studies have evidenced antioxidant activities and/or protective effects of L-ergothioneine under experimental conditions involving oxidative stress, i.e. following stimulation by pro-inflammatory or pro-oxidizing agents/conditions.

Such in vitro properties of L-ergothioneine are summarized below:

  • Protection of bacteriophages T4 and P22 against inactivation induced by γ-irradiation [103].
  • Protection of isolated rat heart from ischemia/reperfusion-induced injury [93].
  • Protection against oxidative damage to macromolecule, including nuclear and mitochondrial DNA, proteins and lipids, induced by:

– reactive oxygen species in HeLa cells [104] and PC12 cells [105],

– peroxynitrite anion in N-18-RE-105 cells [106],

– UV [63] and UVA/visible light [107] in human epidermal keratinocytes,

– UVA in human dermal fibroblasts [108],

– UVB in HaCaT cells [109], 

– β-amyloid peptide in PC12 cells [110].

  • Inhibition of UVB-induced up-regulation of TNF-α expression [111], as well as of UVA-induced MMP-1 [111] and peroxide [62] production in human dermal fibroblasts.
  • Inhibition of UV-induced apoptosis, caspase-9 activity and PARP cleavage in human epidermal keratinocytes [63].
  • Inhibition of β-amyloid peptide-induced apoptosis, caspase-3 activity and PARP cleavage in PC12 cells [110].
  • Inhibition of hydrogen peroxide-induced apoptosis and p38 MAPK phosphorylation in PC12 cells [105].
  • Prevention of cisplatin-induced inhibition of the growth of axon and dendrite in primary cortical neurons [112].
  • Inhibition of hydrogen peroxide- and TNF-α-induced NF-κB activation and IL-8 release in epithelial cells [113].
  • Protection against cell death induced by reactive oxygen species in human brain microvascular endothelial cells [61].
  • Prevention of phosphorylation of NO synthase, and decrease of SOD and catalase activities induced by oxidized LDL in human umbilical vein endothelial cells (HUVECs) [114].
  • Inhibition of oxidized LDL-induced apoptosis of HUVECs, in association with inhibiting Bax activation, Bcl-2 downregulation and caspase-3 activity elicited by oxidized LDL [114].
  • Inhibition of oxidized LDL-induced p38 phosphorylation and NFκB activation in HUVECs, substantiated by the inhibition of the expression of cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin), and subsequent monocyte binding [114]. This inhibitory effect of L-ergothioneine on monocyte adhesion was also demonstrated in human artery endothelial cells following IL-1β stimulation [115].
  • Inhibition of IL-6 production by C2C12 myoblasts [116] and 3T3-L1 adipocytes [117] following stimulation by palmitic acid and TNF-α, respectively.
  • Inhibition of mushroom polyphenoloxidase activity [118].

Some protective effects of L-ergothioneine against oxidative stress-induced injury were not confirmed [21,119], owing to differing experimental conditions and/or concentrations used.

Furthermore, consistently with its in vitro antioxidant properties, L-ergothioneine has been shown to improve food preservation by preventing discoloration and lipid peroxidation of meat [118,120].

Interestingly, a recent study on neural progenitor cells has demonstrated that L-ergothioneine inhibits cell proliferation and promotes neuronal differentiation, in correlation with inhibiting the intracellular production of reactive oxygen species and up-regulating Math1 gene, respectively [64].

With respect to reproduction, the following effects of L-ergothioneine have been described:

  • Decrease of the inhibitory effect of p-chloromercuribenzoic acid on spermatozoa respiration in the guinea pig [121].
  • Increase in the acrosome reaction of guinea pig spermatozoa, and increase in the fertility of mouse spermatozoa, both in vitro and in vivo in the latter case [122].
  • Increase in the oocyte maturation and embryonic development in the ewe [123].
  • Increase in spermatozoa preservation in the guinea pig [121], stallion [124] and ram [125-127].

In vivo protective effects of L-ergothioneine are summarized below:

  • Protection of N. crassa conidia against peroxide damage during germination, and improvement of their longevity [12,128].
  • Decrease of nitrite-induced methemoglobin formation in rabbits [129] and rats [130].
  • Prevention of the teratogenic effects of cadmium in mice [131].
  • Protection against ethionine-induced liver injury in rats [132].
  • Decrease of the rate of embryo malformation in diabetic rats [133].
  • Protection against ischemia/reperfusion-induced injury in rat liver [134] and small intestine [135].
  • Protection against oxidative damage induced by ferric-nitrilotriacetate in rat liver and kidney [136].
  • Neuroprotection against NMDA excitotoxicity in rats [137].
  • Neuroprotection against cisplatin [112], β-amyloid [138] and D-galactose [139] toxicity in mice.
  • Protection against cytokine-induced lung inflammation and injury in rats [140].
  • Prevention of streptozotocin-induced impairment of relaxation to acetylcholine in rat artery [61].

Through these in vivo studies, it was in particular shown that L-ergothioneine treatment, with respect to no treatment, resulted in decreasing lipid peroxidation, saving endogenous antioxidant defenses, such as vitamin E and glutathione, and protecting tissue against oxidative stress-induced injury.

No clinical data have been published to date regarding the effect of specifically administering pure Lergothioneine in humans. However, the following interesting observations, sometimes contradictory, have been reported in humans on the variation of L-ergothioneine concentration in various pathological conditions associated with an inflammatory process, compared to that of healthy control subjects:

  • Decrease of L-ergothioneine concentration in erythrocyte of patients with chronic myeloid leukemia [141].
  • Decrease  of L-ergothioneine concentration in the lens eye of cataract patients, and all the more when the degree of cataract is high [48].
  • Decrease [142] or increase [143] of L-ergothioneine concentration in erythrocyte of patients with rheumatoid arthritis.
  • Increase of L-ergothioneine concentration in erythrocyte of women in pre-eclampsia condition [144].
  • Decrease [42] and increase [145] of L-ergothioneine concentration in erythrocyte and intestinal mucosa, respectively, of patients with Crohn's disease.
  • Decrease of the seric concentration of L-ergothioneine in patients with Parkinson's disease [146].

Future studies will be needed to better understand the origin of these variations and to assess their clinical interest.

 

Viewpoint and perspectives

While many studies continue to highlight protective effets of L-ergothioneine under experimental conditions involving oxidative stress, the exact role of L-ergothioneine remains unknown today. It has been suggested that L-ergothioneine may represent a new vitamin [104], but its essential role has not been discovered yet through deprivation or knockout in vivo studies, the resulting animals being phenotypically similar to control animals. Such an essential role might be only displayed after a longer period of observation and/or under stress conditions.

In this context, it is essential to emphasize the increase sensitivity to oxidative stress that has been reported in OCTN1/ETT-knockdown cells [104], OCTN1/ETT-knockout mice [42,76], and OCTN1/ETT-knockout zebrafish [74], as well as in microorganisms whose ability to produce L-ergothioneine was prevented by disruption of a biosynthetic gene [147].  

Given its tissue absorption by a specific transporter, its in vivo protective effects, and the results of knockdown/knockout studies, L-ergothioneine can at least be considered as a physiological antioxidant endowed with anti-inflammatory properties.

However, naming L-ergothioneine an "antioxidant" might be confusing if this property is only related to its ability to scavenge reactive oxygen/nitrogen species. Indeed, chemically speaking, L-ergothioneine is a weak reducing agent at physiological pH, due to the fact that its thione tautomeric form predominates at these pH [148]. This accounts in particular for its stability towards oxygen in aqueous solution, which distinguishes it from other biological thiols such as glutathione and dihydrolipoic acid.

In a biological context, another antioxidant mechanism may account for the protective effects of L-ergothioneine. It is related to the ability of L-ergothioneine to specifically interact with proteins. It is implicit when considering its transporter, and it has recently been described for the first time in the case of a bacterial enzyme for which L-ergothioneine is used as co-factor [149]. This putative mechanism remains to be investigated in regard to redox alterations of protein cysteine residues, such as disulfide formation, nitrosylation and metal coordination. It is now well established that these reversible chemical modifications play a key role in the redox signaling of cellular events and cell fate. So in that case, defining L-ergothioneine as a modulator of redox homeostasis would be more appropriate to describe its antioxidant mechanism of action.

Tissue absorption of L-ergothioneine by a specific transporter implies a beneficial role of this unique micronutrient. Furthermore, L-ergothioneine has  been shown to be not mutagenic, nor genotoxic [150,151], and without an adverse effect on a broad range of reproductive parameters [152]. Its good tolerance was also exemplified in investigating various health indications [153-155]. A better understanding of its role requires more studies and deserves further attention with regard to human health, in particular as micronutrient deficiencies may increase the risk of developing age-related disorders and diseases [156-158]. Their development is correlated with a mild pro-inflammatory state in which oxidative stress, i.e. disruption of redox signaling and control [159], plays a major role.

This has led Tetrahedron to develop a novel industrial process (WO2011042480), using a biomimetic and sustainable approach [160], to make L-ergothioneine available and to supply it in bulk quantities. Tetrahedron supplies L-ergothioneine for Research and can propose a GMP quality product whose characterization and safety have been assessed according to regulatory requirements for its use as a nutritional ingredient in humans.

For more information on our product, please contact us.

 

References

  1. New base obtained from ergot of rye. Ergothioneine – TANRET C. – 1909 – C. R. Acad. Sci., 149:222-224
  2. Biosynthesis of ergothioneine and hercynine by mycobacteria – GENGHOF D.S., and VAN DAMME O. – 1964 – J. Bacteriol., 87(4):852-862
  3. Cyanobacteria produce high levels of ergothioneine – PFEIFFER C., BAUER T., SUREK B., SCHÖMIG E., and GRÜNDEMANN D. – 2011 – Food Chem., 129(4):1766-1769
  4. Ergothioneine in microorganisms – MELVILLE D.B., GENGHOF D.S., INAMINE E., and KOVALENKO V. – 1956 – J. Biol. Chem., 223(1):9-17
  5. Ergothioneine – MELVILLE D.B. – 1959 – Vitam. Horm., 17:155-204
  6. Biosynthesis of ergothioneine and hercynine by fungi and Actinomycetales – GENGHOF D.S. – 1970 – J. Bacteriol., 103(2):475-478
  7. Influence of selected cultural factors and postharvest storage on ergothioneine content of common button mushroom – DUBOST N.J., BEELMAN R.B., and ROYSE D.J. – 2007 – Int. J. of Med. Mushrooms, 9:163-176
  8. Supplementation of methionine enhanced the ergothioneine accumulation in the Ganoderma neo-japonicum mycelia – LEE W.Y., PARK E-J., and AHN J.K. – 2008 – Appl. Biochem. Biotechnol., 158(1):213-221
  9. Mycobial enhancement of ergothioneine by submerged cultivation of edible mushroom mycelia and its application as an antioxidative compound – TEPWONG P., GIRI A., SASAKI F., FUKUI R., and OHSHIMA T. – 2012 – Food Chem., 131:247-258
  10. The enzymatic α-N-methylation of histidine – ISHIKAWA Y., and MELVILLE D.B. – 1970 – J. Biol. Chem., 245(22):5967-5973
  11. Participation of an intermediate sulfoxide in the enzymatic thiolation of the imidazole ring of hercynine to form ergothioneine – ISHIKAWA Y., ISRAEL S.E., and MELVILLE D.B. – 1974 – J. Biol. Chem., 249(14):4420-4427
  12. The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination – BELLO M.H., BARRERA-PEREZ V., MORIN D., and EPSTEIN L. – 2012 – Fung. Gen. Biol., 49(2):160-172
  13. In vitro reconstruction of mycobacterial ergothioneine biosynthesis – SEEBECK F.P. – 2010 – JACS, 132(19):6632-6633
  14. [Incidence of herzynine, ergothioneine, homarine, trigonelline, glycocoll betaine, choline, trimethylamine, adenine and almost all amino acids of proteins in Limulus polyphemus L] – ACKERMANN D., and LIST P.H. – 1958 – Hoppe Seylers Z. Physiol. Chem., 313:30-36
  15. The uptake of ergothioneine from the soil into the latex of Hevea brasiliensis – AUDLEY B.G., and TAN C.H. – 1968 – Phytochemistry, 7(11):1999-2000
  16. Ergothioneine accumulation in a medicinal plant Gastrodia elata – PARK E-J., LEE W.Y., KIM S.T., AHN J.K., and BAE E.K. – 2010 – J. Med. Plants Res., 4(12):1141-1147
  17. On the origin of animal ergothioneine – MELVILLE D.B., OTKEN C.C., and KOVALENKO V. – 1955 – J. Biol. Chem., 216:325-331
  18. The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation – WEIGAND-HELLER A.J., KRIS-ETHERTON P.M., and BEELMAN R.B. – 2012 – Prev. Med., 54(Suppl.):S75-78
  19. Blood ergothioneine in the germ-free chicken – MELVILLE D.B., and HORNER W.H. – 1953 – J. Biol. Chem., 202(1):187-191
  20. Studies on ergothioneine. II. Origin of ergothioneine in the animal organs – KONISHI T., TAMAKI N., TUNEMORI F., MASUMITU N., OKUMURA H., and HAMA T. – 1972 – Vitamins, 46(3):127-130
  21. Dietary sources and antioxidant effects of ergothioneine – EY J., SCHÖMIG E., and TAUBERT D. – 2007 – J. Agric. Food Chem., 15(16):6466-6474
  22. Quantification of polyphenols and ergothioneine in cultivated mushrooms and correlation to total antioxidant capacity – DUBOST N.J., OU B., and BEELMAN R. – 2007 – Food Chem., 105(2):727-735
  23. The occurrence of ergothioneine in plant material – MELVILLE D.B., and EICH S. – 1956 – J. Biol. Chem., 218:647-651
  24. Ergothioneine and hercynine in Hevea brasiliensis latex – TAN C.H., and AUDLEY B.G. – 1968 – Phytochemistry, 7(1):109-118
  25. On ergothioneine in blood and diazo-reacting substances in maize – HUNTER G. – 1951 – Biochem. J., 48(3):265-270
  26. Studies on the metabolism of semen. VIII. Ergothioneine as a normal constituent of boar seminal plasma. Purification and crystallization. Site of formation and function – MANN T., and LEONE E. – 1953 – Biochem. J., 53(1):140-148
  27. A method for the determination of ergothioneine in blood – MELVILLE D.B., and LUBSCHEZ R. – 1953 – J. Biol. Chem., 200(1):275-285
  28. Tissue ergothioneine – MELVILLE D.B., HORNER W.H., and LUBSCHEZ R. – 1954 – J. Biol. Chem., 206(1):221-228
  29. Further studies on seminal ergothioneine of the pig – HEATH H., RIMINGTON C., and MANN T. – 1957 – Biochem. J., 65(2):369-373
  30. Semen composition and metabolism in the stallion and jackass – MANN T., MINOTAKIS C.S., and POLGE C. – 1963 – J. Reprod. Fertil., 5:109-122
  31. Ergothioneine in the central nervous system – BRIGGS I. – 1972 – J. Neurochem., 19(27):27-35
  32. Studies on ergothioneine. I. Distribution in the body and the subcellular fractions of liver – HAMA T., KONISHI T., TAMAKI N., TUNEMORI F., and OKUMURA H. – 1972 – Vitamins, 46(3):121-126
  33. Characteristics of the successive jets of ejaculated semen of stallions – KOSINIAK K. – 1975 – J. Reprod. Fertil. Suppl., 23:59-61
  34. Biochemistry of stallion semen – MANN T. – 1975 – J. Reprod. Ferti. Suppl., 23:47-52
  35. Studies on ergothioneine. V. Determination by High Performance Liquid Chromatography and application to metabolic research – MAYUMI T., KAWANO H., SAKAMOTO Y., SUEHISA E., KAWAI Y., and HAMA T. – 1978 – Chem. Pharm. Bull., 26(12):3772-3778
  36. Biochemical components of stallion seminal plasma before and after the breeding season – KOSINIAK K., and BITTMAR A. – 1981 – Anim. Reprod. Sci., 4(1):39-47
  37. Comparison of the 1H and 31P NMR spectra of erythrocytes and plasma from some Australian native animals: Bandicoot, Echidna, Koala, Little Penguin, Tammar Wallaby, Tasmanian Devil, Tree Kangaroo and Wombat – RAE C., SWEENEY K.J.E., KROCKENBERGER A.K., AGAR N.S., GALLAGHER C.H., and KUCHEL P.W. – 1993 – Comp. Haematol. Int., 3(2):71-80
  38. Influence of age and season on certain biochemical constituents of seminal plasma of Arabian horses – ABOU-AHMED M.M., EL-BELELY M.S., ISMAIL S.T., EL-BAGHDADY Y.R.M., and HEMEIDA N.A. – 1993 – Anim. Reprod. Sci., 32(3-4):237-244
  39. Ergothioneine distribution in bovine and porcine ocular tissues – SHIRES T.K., BRUMMEL M.C., PULIDO J.S., and STEGINK L.D. – 1997 – Comp. Biochem. Physiol. C. Pharmacol. Toxicol. Endocrinol., 117(1):117-120
  40. A note on antioxidant capacity of boar seminal plasma – STRZEZEK J., LAPKIEWICZ S., and LECEWICZ M. – 1999 – Anim. Sci. Pap. Rep., 17(4):181-188
  41. Characteristics of antioxidant system in dog semen – STRZEZEK R., KOZIOROWSKA-GILUN M., KOWALOWKA M., and STRZEZEK J. – 2009 – Polish J. Vet. Sci., 12(1):55-60
  42. Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1 – KATO Y., KUBO Y., IWATA D., KATO S., SUDO T., SUGIURA T., KAGAYA T., WAKAYAMA T., HIRAYAMA A., SUGIMOTO M., SUGIHARA K., KANEKO S., SOGA T., ASANO M., TOMITA M., MATSUI T., WADA M., and TSUJI A. – 2010 – Pharm. Res., 27(5):832-840
  43. Antioxidant defence system of boar cauda epididymidal spermatozoa and reproductive tract fluids – KOZIOROWSKA-GILUN M., KOZIOROWSKI M., FRASER L., and STRZEZEK J. – 2011 – Reprod. Dom. Anim., 46(3):527-533
  44. Paramount levels of ergothioneine transporter SLC22A4 MRNA in boar seminal vesicles and cross-species analysis of ergothioneine and glutathione in seminal plasma – NIKODEMUS D., LAZIC D., BACH M., BAUER T., PFEIFFER C., WILTZER L., LAIN E., SCHÖMIG E., and GRÜNDEMANN D. – 2011 – J. Physiol. Pharmacol., 62(4):411-419
  45. Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation – NAKAMICHI N., TAGUCHI T., HOSOTANI H., WAKAYAMA T., SHIMIZU T., SUGIURA T., ISEKI S., and KATO Y. – 2012 – Neurochem. Int., 61(7):1121-1132
  46. Ultra-performance liquid chromatographic determination of L-ergothioneine in commercially available classes of cow milk – SOTGIA S., PISANU E., CAMBEDDA D., PINTUS G., CARRU C., and ZINELLU A. – 2014 – J. Food Sci., 79(9):C1683-1687
  47. Relationship between nonprotein sulfhydryl concentration of seminal fluid and motility of spermatozoa in man – HAAG F.M., and MacLEOD J. – 1959 – J. Appl. Physiol., 14(1):27-30
  48. Ergothioneine content in normal and senile human cataractous lenses – SHUKLA Y., KULSHRESTHA O.P., and KHUTETA K.P. – 1981 – Indian J. Med. Res., 73:472-473
  49. L-ergothioneine level in red blood cells of healthy human males in the Western province of Saudi Arabia – KUMOSANI T.A. – 2001 – Exp. Mol. Med., 33(1):20-22
  50. Quantification of L-ergothioneine in human plasma and erythrocytes by liquid chromatography-tandem mass spectrometry – WANG L-Z., THUYA W-L., TOH D.S-L., LIE M.G-L., LAU J-Y.A., KONG L-R., WAN S-C., CHUA K-N., LEE E.J-D., and GOH B-C. – 2012 – J. Mass Spectrom., 48:406-412
  51. Clinical and biochemical correlates of serum L-ergothioneine concentrations in community-dwelling middle-aged and older adults – SOTGIA S., ZINELLU A., MANGONI A.A., PINTUS G., ATTIA J., CARRU C., and McEVOY M. – 2014 – PLoS ONE, 9(1):e84918
  52. Ergothioneine; antioxidant potential, physiological function and role in disease – CHEAH I.K., and HALLIWELL B. – 2012 – Biochim. Biophys. Acta, 1822(5):784-793
  53. Discovery of the ergothioneine transporter – GRÜNDEMANN D., HARLFINGER S., GOLZ S., GEERTS A., LAZAR A., BERKELS R., JUNG N., RUBBERT A., and SCHÖMIG E. – 2005 – PNAS, 102(14):5256-5261
  54. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1 – TAMAI I., YABUUCHI H., NEZU J., SAI Y., OKU A., SHIMANE M., and TSUJI A. – 1997 – FEBS Lett., 419(1):107-111
  55. Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations – YABUUCHI H., TAMAI I., NEZU J., SAKAMOTO K., OKU A., SHIMANE M., SAI Y., and TSUJI A. – 1999 – J. Pharmacol. Exp. Therap., 289(2):768-773
  56. Probing the substrate specificity of the ergothioneine transporter with methimazole, hercynine, and organic cations – GRIGAT S., HARLFINGER S., PAL S., STRIEBINGER R., GOLZ S., GEERTS A., LAZAR A., SCHÖMIG E., and GRÜNDEMANN D. – 2007 – Biochem. Pharmacol., 74(2):309-316
  57. Expression of organic cation transporter OCTN1 in hematopoietic cells during erythroid differentiation – KOBAYASHI D., AIZAWA S., MAEDA T., TSUBOI I., YABUUCHI H., NEZU J., TSUJI A., and TAMAI I. – 2004 – Exp. Hematol., 32(12):1156-1162
  58. An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis – TOKUHIRO S., YAMADA R., CHANG X., SUZUKI A., KOCHI Y., SAWADA T., SUZUKI M., NAGASAKI M., OHTSUKI M., ONO M., FURUKAWA H., NAGASHIMA M., YOSHINO S., MABUCHI A., SEKINE A., SAITO S., TAKAHASHI A., TSUNODA T., NAKAMURA Y., and YAMAMOTO K. – 2003 – Nat. Genet., 35(4):341-348
  59. Transport of organic cations across the blood-testis barrier – MAEDA T., GOTO A., KOBAYASHI D., and TAMAI I. – 2007 – Mol. Pharm., 4(4):600-607
  60. Involvement of carnitine/organic cation transporter OCTN2 (SLC22A5) in distribution of its substrate carnitine to the heart – IWATA D., KATO Y., WAKAYAMA T., SAI Y., KUBO Y., ISEKI S., and TSUJI A. – 2008 – Drug Metab. Pharmacokinet., 23(3):207-215
  61. Uptake and protective effects of ergothioneine in human endothelial cells – LI R.W.S., YANG C., SIT A.S.M., KWAN Y.W., LEE S.M.Y., HOI M.P.M., CHAN S.W., HAUSMN M., VANHOUTTE P.M., and LEUNG G.P.H. – 2014 – J. Pharmacol. Exp. Ther., 350(3):691-700
  62. A comparison of the relative antioxidant potency of L-ergothioneine and idebenone – DONG K.K., DAMAGHI N., KIBITEL J., CANNING M.T., SMILES K.A., and YAROSH D.B. – 2007 – J. Cosmet. Dermatol., 6(3):183-188
  63. Skin cells and tissue are capable of using L-ergothioneine as an integral component of their antioxidant defense system – MARKOVA N.G., KARAMAN-JURUKOVSKA N., DONG K.K., DAMAGHI N., SMILES K.A., and YAROSH D.B. – 2009 – Free Radic. Biol. Med., 46(8):1168-1176
  64. Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons – ISHIMOTO T., NAKAMICHI N., HOSOTANI H., MASUO Y., SUGIURA T., and KATO Y. – 2014 – PLoS ONE, 9(2):e89434
  65. Involvement of OCTN1 (SLC22A4) in pH-dependent transport of organic cations – TAMAI I., NAKANISHI T., KOBAYASHI D., CHINA K., KOSUGI Y., NEZU J-I., SAI Y., and TSUJI A. – 2004 – Mol. Pharm., 1(1):57-66
  66. Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway – HORVATH G., SCHMID N., FRAGOSO M.A., SCHMID A., CONNER G.E., SALATHE M., and WANNER A. – 2007 – Am. J. Respir. Cell Mol. Biol., 36(1):53-60
  67. Evaluation of air-interfaced Calu-3 cell layers for investigation of inhaled drug interactions with organic cation transporters in vitro – MUKHERJEE M., PRITCHARD D.I., and BOSQUILLON C. – 2012 – Int. J. Pharm., 426(1-2):7-14
  68. Expression and localization of carnitine/organic cation transporter OCTN1 and OCTN2 in ocular epithelium – GARRETT Q., XU S., SIMMONS P.A., VEHIGE J., FLANAGAN J.L., and WILLCOX M.D. – 2008 – Invest. Ophthalmol. Vis. Sci., 49(11):4844-4849
  69. Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver – SUGIURA T., KATO S., SHIMIZU T., WAKAYAMA T., NAKAMICHI N., KUBO Y., IWATA D., SUZUKI K., SOGA T., ASANO M., ISEKI S., TAMAI I., TSUJI A., and KATO Y.– 2010 – Drug Metab. Dispos., 38(10):1665-1672
  70. Organic cation transporters in human nasal primary culture: expression and functional activity – SHAO D., MASSOUD E., ANAND U., PARIKH A., COWLEY E., CLARKE D., and AGU R.U. – 2013 – Ther. Deliv., 4(4):439-451
  71. Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria – LAMHONWAH A.M., and TEIN I. – 2006 – Biochem. Biophys. Res. Commun., 345(4):1315-1325
  72. The ergothioneine transporter controls and indicates ergothioneine activity--a review – GRÜNDEMANN D. – 2012 – Prev. Med., 54(Suppl.):S71-S74
  73. Untersuchung der Funktion von Ergothionein durch Knockout des Ergothionein-Transporters des Zebrafisches Danio rerio – PFEIFFER C. – Inaugural Dissertation. Düsseldorf, Oktober 2012
  74. Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels – PFEIFFER C., BACH M., BAUER T., CAMPOS da PONTE J., SCHÖMIG E., and GRÜNDEMANN D. – 2015 – Free Radic. Biol. Med., http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.026
  75. Mechanism of the regulation of organic cation/carnitine transporter 1 (SLC22A4) by rheumatoid arthritis-associated transcriptional factor RUNX1 and inflammatory cytokines – MAEDA T., HIRAYAMA M., KOBAYASHI D., MIYAZAWA K., and TAMAI I. – 2007 – Drug Metab. Dispos., 35(3):394-401
  76. Organic cation transporter Octn1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice – SHIMIZU T., MASUO Y., TAKAHASHI S., and KATO Y. – 2015 – Drug Metab. Pharmacokinet., doi:10.1016/j.dmpk.2015.02.003
  77. Association of SLC22A4 gene polymorphism with rheumatoid arthritis in the Chinese population – REN T-L., HAN Z-J., YANG C-J., HANG Y-X., FANG D-Y., WANG K., ZHU X., JI X-J., and ZHOU F-F. – 2014 – J. Biochem. Mol. Toxicol., doi: 10.1002/jbt.21554
  78. Functional variants of OCTN cation transporter genes are associated with Crohn disease – PELTEKOVA V.D., WINTLE R.F., RUBIN L.A., AMOS C.I., HUANG Q., GU X., NEWMAN B., VAN OENE M., CESCON D., GREENBERG G., GRIFFITHS A.M., ST GEORGE-HYSLOP P.H., and SIMINOVITCH K.A. – 2004 – Nat. Gen., 36(5):471-475
  79. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease – TÖRÖK H.-P., GLAS J., TONENCHI L., LOHSE P., MÜLLER-MYHSOK B., LIMBERSKY O., NEUGEBAUER C., SCHNITZLER F., SEIDERER J., TILLACK C., BRAND S., BRÜNNLER G., JAGIELLO P., EPPLEN J. T., GRIGA T., KLEIN W., SCHIEMONN U., FOLWACZNY M., OCHSENKÜHN T., and FOLWACZNY C. – 2005 – Gut, 54(10):1421-1427
  80. Functional role of the 503F variant of the organic cation transporter OCTN1 in Crohn's disease – TAUBERT D., GRIMBERG G., JUNG N., RUBBERT A., and SCHÖMIG E. – 2005 – Gut, 54(10):1505-1506
  81. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease – SILVERBERG M.S., DUERR R.H., BRANT S.R., BROMFIELD G., DATTA L.W., JANI N., KANE S.V., ROTTER J.I., PHILIP SCHUMM L., HILLARY STEINHART A., TAYLOR K.D., YANG H., CHO J.H., RIOUX J.D., and DALY M.J. – 2007 – Eur. J. Hum. Genet., 15(3):328-335
  82. Crohn's disease and genetic hitchhiking at IBD5 – HUFF C.D., WITHERSPOON D.J., ZHANG Y., GATENBEE C., DENSON L.A., KUGATHASAN S., HAKONARSON H., WHITING A., DAVIS C.T., WU W., XING J., WATKINS W.S., BAMSHAD M.J., BRADFIELD J.P., BULAYEVA K., SIMONSON T.S., JORDE L.B., and GUTHERY S.L. – 2012 – Mol. Biol. Evol., 29(1):101-111
  83. Decreased proliferation and erythroid differentiation of K562 cells by siRNA-induced depression of OCTN1 (SLC22A4) Transporter Gene – NAKAMURA T., SUGIURA S., KOBAYASHI D., YOSHIDA K., YABUUCHI H., AIZAWA S., MAEDA T., and TAMAI I. – 2007 – Pharm. Res., 24(9):1628-1635
  84. Some effects of administering ergothioneine to rats – HEATH H., RIMINGTON C., SEARLE C. E., and LAWSON A. – 1952 – Biochem. J., 50(4):530-533
  85. The effect of age, sex and androgen on blood ergothioneine – MacKENZIE J.B., and MacKENZIE C.G. – 1957 – J. Biol. Chem., 225(2):651-658
  86. Studies on ergothioneine. VI. Distribution and fluctuations of ergothioneine in rats – KAWANO H., OTANI M., TAKEYAMA K., KAWAI Y., MAYUMI T., and HAMA T. – 1982 – Chem. Pharm. Bull., 30(5):1760-1765
  87. Transfer of ergothioneine to newborn and weanling rats – ONTKO J.A., and PHILLIPS P.H. – 1957 – Fed. Proceedings, 16(1):229
  88. Acute administration of Cefepime lowers L-carnitine concentrations in early lactation stage rat milk – LING B., and ALCORN J. – 2008 – J. Nutr., 138:1317-1322
  89. Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids – GILCHRIST S.E., and ALCORN J. – 2010 – Fundam. Clin. Pharmacol., 24(2):205-214
  90. The antioxidant action of ergothioneine – AKANMU D., CECCHINI R., ARUOMA O.I., and HALLIWELL B. – 1991 – Arch. Biochem. Biophys., 288(1):10-16
  91. Antioxidant action of ergothioneine: Assessment of its ability to scavenge peroxynitrite – ARUOMA O.I., WHITEMAN M., ENGLAND T.G., and HALLIWELL B. – 1997 – Biochem. Biophys. Res. Comm., 231(2):389-391
  92. An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox – FRANZONI F., COLOGNATO R., GALETTA F., LAURENZA I., BARSOTTI M., DI STEFANO R., BOCCHETTI R., REGOLI F., CARPI A., BALBARINI A., MIGLIORE L., and SANTORO G. – 2006 – Biomed. Pharmacother., 60(8):453-457
  93. The reduction of ferryl myoglobin by ergothioneine: a novel function for ergothioneine – ARDUINI A., EDDY L., and HOCHSTEIN P. – 1990 – Arch. Biochem. Biophys., 281(1):41-43
  94. Deactivation of singlet molecular oxygen by thiols and related compounds, possible protectors against skin photosensitivity – ROUGEE M., BENSASSON R.V., LAND E.J., and PARIENTE R. – 1988 – Photochem. Photobiol., 47(4):485-489
  95. Quenching of singlet molecular oxygen by carnosine and related antioxidants. Monitoring 1270-nm phosphorescence in aqueous media – EGOROV S.Y., KURELLA E.G., BOLDYREV A.A., and KRASNOVSKY A.A. Jr – 1997 – Biochem. Mol. Biol. Int., 41(4):687-694
  96. Some prevalent biomolecules as defenses against singlet oxygen damage – DAHL T.A., MIDDEN W.R., and HARTMAN P.E. – 1988 – Photochem. Photobiol., 47(3):357-362
  97. Interaction of ergothioneine with metal ions and metalloenzymes – HANLON D.P. – 1971 – J. Med. Chem., 14(11):1084-1087
  98. Metal complexes of ergothioneine – MOTOHASHI N., MORI I., SUGIURA Y., and TANAKA H. – 1974 – Chem. Pharm. Bull., 22(3):654-657
  99. Complexing of copper ion by ergothioneine – MOTOHASHI N., MORI I., and SUGIURA Y. – 1976 – Chem. Pharm. Bull., 24(10):2364-2368
  100. 2-Imidazolethiones protect ascorbic acid from oxidation induced by copper – SMITH R.C., and GORE J.Z. – 1990 – Biochim. Biophys. Acta, 1034(3):263-267
  101. Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex – ZHU B.Z., MAO L., FAN R.M., ZHU J.G., ZHANG Y.N., WANG J., KALYANARAMAN B. and FREI B. – 2010 – Chem. Res. Toxicol., 24(1):30-34
  102. A density functional theory investigation into the binding of the antioxidants ergothioneine and ovothiol to copper – De LUNA P., BUSHNELL E.A.C., and GAULD J.W. – 2013 – J. Phys. Chem. A, 117(19):4057-4065
  103. Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22 – HARTMAN P.E., HARTMAN Z., and CITARDI M.J. – 1988 – Radiat. Res., 114(2):319-330
  104. The unusual amino acid L-ergothioneine is a physiologic cytoprotectant – PAUL B.D., and SNYDER S.H. – 2010 – Cell Death Differ., 17(7):1134-1140
  105. Modulation of hydrogen peroxide-induced DNA damage, MAPKs activation and cell death in PC12 by ergothioneine – COLOGNATO R., LAURENZA I., FONTANA I., COPPEDÉ F., SICILIANO G., COECKE S., ARUOMA O.I., BENZI L., and MIGLIORE L. – 2006 – Clin. Nutr., 25(1):135-145
  106. Protection against oxidative damage and cell death by the natural antioxidant ergothioneine – ARUOMA O.I., SPENCER J.P., and MAHMOOD N. – 1999 – Food Chem. Toxicol., 37(11):1043-1053
  107. Genotoxicity of visible light (400-800 nm) and photoprotection assessment of ectoin, L-ergothioneine and mannitol and four sunscreens – BOTTA C., Di GIORGIO C., SABATIER A.S., and De MÉO M. – 2008 – J. Photochem. Photobiol. B: Biology, 91(1):24-34
  108. L-Ergothioneine protects skin cells against UV-induced damage - A preliminary study – BAZELA K., SOLYGA-ZUREK A., DEBOWSKA R., ROGIEWICZ K., BARTNIK E., and ERIS I. – 2014 – Cosmetics, 1:51-60
  109. Protective effect of trehalose-loaded liposomes against UVB-induced photodamage in human keratinocytes – EMANUELE E., BERTONA M., SANCHIS-GOMAR F., PAREJA-GALEANO H., and LUCIA A. – 2014 – Biomed. Rep., 2(5):755-759
  110. Ergothioneine rescues PC12 cells from beta-amyloid-induced apoptotic death – JANG J.H., ARUOMA O.I., JEN L.S., CHUNG H.Y., and SURH YJ. – 2004 – Free Radic. Biol. Med., 36(3):288-299
  111. L-Ergothioneine scavenges superoxide and singlet oxygen and supresses TNF-α and MMP-1 expression in UV-irradiated human dermal fibroblasts – OBAYASHI K., KURIHARA K., OKANO Y., MASAKI H., and YAROSH D.B. – 2005 – J. Cosmet. Sci., 56(1):17-27
  112. Ergothioneine protects against neuronal injury induced by cisplatin both in vitro and in vivo – SONG T.Y., CHEN C.L., LIAO J.W., OU H.C., and TSAI M.S. – 2010 – Food Chem. Toxicol., 48(12):3492-3499
  113. Ergothioneine inhibits oxidative stress- and TNF-α-induced NF-κB activation and interleukin-8 release in alveolar epithelial cells – RAHMAN I., GILMOUR P.S., JIMENEZ L.A., BISWAS S.K., ANTONICELLI F., and ARUOMA O.I. – 2003 – Biochem. Biophys. Res. Commun., 302(4):860-864
  114. Ergothioneine represses inflammation and dysfunction in human endothelial cells exposed to oxidized low-density lipoprotein – SAING L., WEI YC., and TSENG CJ. – 2015 – Clin. Exp. Pharmacol? Physiol., doi: 10.1111/1440-1681.12374
  115. The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease – MARTIN K.R. – 2010 – J. Med. Food, 13(6):1340-1346
  116. Modulation of palmitic acid-induced cell death by ergothioneine: Evidence of an anti-inflammatory action – LAURENZA I., COLOGNATO R., MIGLIORE L., DEL PRATO S., and BENZI L. – 2008 – Biofactors, 33(4):237-247
  117. Ergothioneine as an anti-oxidative/anti-inflammatory component in several edible mushrooms – ITO T., KATO M., TSUCHIDA H., HARADA E., NIWA T., and OSAWA T. – 2011 – Food Sci. Technol. Res., 17(2):103-110
  118. Effects of ergothioneine from mushrooms (Flammulina velutipes) on melanosis and lipid oxidation of kuruma shrimp (Marsupenaeus japonicus) – ENCARNACION A.B., FAGUTAO F., HIRONO I., USHIO H., and OHSHIMA T. – 2010 – J. Agric. Food Chem., 58(4):2577-2585
  119. In vitro administration of ergothioneine failed to protect isolated ischaemic and reperfused rabbit heart – CARGNONI A., BERNOCCHI P., CECONI C., CURELLO S., and FERRARI R. – 1995 – Biochim. Biophys. Acta, 1270(2-3):173-178
  120. Antioxidative activity and antidiscoloration efficacy of ergothioneine in mushroom (Flammulina velutipes) extract added to beef and fish meats – BAO H.N., USHIO H., and OHSHIMA T. – 2008 – J. Agric. Food Chem., 56(21):10032-10040
  121. Studies on ergothioneine. IV. Effect of ergothioneine upon spermatozoa from guinea pigs – HAMA T., OKUMURA H., TAMAKI N., and KONISHI T. – 1973 - Yakugaku Zasshi, 93(3):369-373
  122. Studies on ergothioneine. IX. Ergothioneine stimulates mouse spermatozoa and fertilization in vitro – MAYUMI T., KAWANO H., KAWAI Y., and HAMA T. – 1984 – Dev. Growth Differ., 26(6):563-569
  123. The effects of L-ergothioneine and L-ascorbic acid on the in vitro maturation (IVM) and embryonic development (IVC) of sheep oocytes – ÖZTÜRKLER Y., YILDIZ S., GÜNGÖR O., PANCARCI S.M., KACAR C., and ARI U.C. – 2010 – Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 16(5):757-763
  124. Technologie de la conservation du sperme chez plusieurs vertébrés domestiques: protection des lipides membranaires, intégrité du noyau et élargissement des méthodes – LABBE C., BLESBOIS E., LEBOEUF B., MARTORIATI A., GUILLOUET P., STRADAIOLI G., and MAGISTRINI M. – 2003 – Les actes du BRG, 4:143-157
  125. Effects of cysteine and ergothioneine on post-thawed Merino ram sperm and biochemical parameters – ÇOYAN K., BASPINAR N., BUCAK M.N., and AKALIN P.P. – 2011 – Cryobiology, 63(1):1-6
  126. Ergothioneine attenuates the DNA damage of post-thawed Merino ram sperm – ÇOYAN K., BUCAK M.N., BASPINAR N., TASPINAR M., and AYDOS S. – 2012 – Small Rumin. Res.,106(2-3):165-167
  127. Effect of L-(+)-ergothioneine (EGT) on freezability of ram semen – ARI U.C., KULAKSIZ R., OZTURKLER Y., YILDIZ S., and LEHIMCIOGLU N.C. – 2012 – Int. J. Anim. Vet. Adv., 4(6):378-383
  128. Endogenous ergothioneine is required for wild type levels of conidiogenesis and conidial survival but does not protect against 254 nm UV-induced mutagenesis or kill – BELLO M.H., MOGANNAM J.C., MORIN D., and EPSTEIN L. – 2014 – Fungal Genet. Biol., 73:120-127
  129. Ergothioneine depletion in rabbit erythrocytes and its effect on methemoglobin formation and reversion – SPICER S.S., WOOLEY J.G., and KESSLER V. – 1951 – Proc. Soc. Exp. Biol. Med., 77(3):418-420
  130. The effect of diet on methemoglobin levels of nitrite-injected rats – MORTENSEN R.A. – 1953 – Arch. Biochem. Biophys., 46(1):241-243
  131. Studies on Ergothioneine. VIII. Preventive effects of ergothioneine on cadmium-induced teratogenesis – MAYUMI T., OKAMOTO K., YOSHIDA K., KAWAI Y., KAWANO H., HAMA T., and TANAKA K. – 1982 – Chem. Pharm. Bull., 30(6):2141-2146
  132. Studies on ergothioneine. X. Effects of ergothioneine on the hepatic drug metabolizing enzyme system and on experimental hepatic injury in rats – KAWANO H., CHO K., HARUNA Y., KAWAI Y., MAYUMI T., and HAMA T. – 1983 – Chem. Pharm. Bull., 31(5):1676-1681
  133. Effects of ergothioneine on diabetic embryopathy in pregnant rats – GUIJARRO M.V., INDART A., ARUOMA O.I., VIANA M., and BONET B. – 2002 – Food Chem. Toxicol., 40(12):1751-1755
  134. Ergothioneine pretreatment protects the liver from ischemia-reperfusion injury caused by increasing hepatic heat shock protein 70 – BEDIRLI A., SAKRAK O., MUHTAROGLU S., SOYUER I., GULER I., RIZA ERDOGAN A., and SOZUER E.M. – 2004 – J. Surg. Res., 122(1):96-102
  135. Ergothioneine modulates proinflammatory cytokines and heat shock protein 70 in mesenteric ischemia and reperfusion injury – SAKRAK O., KEREM M., BEDIRLI A., PASAOGLU H., AKYUREK N., OFLUOGLU E., and GÜLTEKIN F.A. – 2007 – J. Surg. Res., 144(1):36-42
  136. L-Ergothioneine modulates oxidative damage in the kidney and liver of rats in vivo: studies upon the profile of polyunsaturated fatty acids – DEIANA M., ROSA A., CASU V., PIGA R., ASSUNTA DESSÌ M., and ARUOMA O.I. – 2004 – Clin. Nutr., 23(2):183-193
  137. Ergothioneine treatment protects neurons against N-methyl-D-aspartate excitotoxicity in an in vivo rat retinal model – MONCASTER J.A., WALSH D.T., GENTLEMAN S.M., JEN L.S. and ARUOMA O.I. – 2002 – Neurosci. Lett., 328(1):55-59
  138. Ergothioneine protects against neuronal injury induced by β-amyloid peptide in mice – YANG N-C., LIN H-C., WU J-H., OU H-C., CHAI Y-C., TSENG C-Y., LIAO J-W., and SONG T-Y. – 2012 – Food Chem. Toxicol., 50(11):3902-3911
  139. Ergothioneine and melatonin attenuate oxidative stress and protect against learning and memory deficits in C57BL/6J mice treated with D-galactose – SONG TY., LIN HC., CHEN CL., WU JH., LIAO JW., and HU ML. – 2014 – Free Radic. Res., 48(9):1049-1060
  140. Effect of Ergothioneine on acute lung injury and inflammation in cytokine insufflated rats – REPINE J.E., and ELKINSN.D. – 2012 – Prev. Med., 54(Suppl.):S79-S82
  141. Unbound amino acid concentrations in plasma, erythrocytes, leukocytes and urine of patients with leukemia – McMENAMY R.H., LUND C.C., and WALLACH D.F.H. – 1960 – J. Clin. Invest., 39(11): 1688-1705
  142. Clinical analysis in intact erythrocytes using 1H spin echo NMR – REGLINSKI J., SMITH W.E., WILSON R., BUCHANAN L.M., McKILLOP J.H., THOMSON J.A., BRZESKI M., MARABANI M., and STURROCK R.D. – 1991 – Clin. Chim. Acta, 201(1-2):45-57
  143. Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study – TAUBERT D., LAZAR A., GRIMBERG G., JUNG T., RUBBERT A., DELANK K.S., PERNIOK A., and SCHÖMIG E. – 2006 – J. Rheumatol., 33(11):2139-2145
  144. Imidazole-based erythrocyte markers of oxidative stress in preeclampsia: An NMR investigation – TURNER E., BREWSTER J.A., SIMPSON N.A., WALKER J.J., and FISHER J. – 2009 – Reprod. Sci., 16(11):1040-1051
  145. Increased ergothioneine tissue concentrations in carriers of the Crohn's disease risk-associated 503F variant of the organic cation transporter OCTN1 – TAUBERT D., JUNG N., GOESER T., and SCHÖMIG E. – 2009 – Gut., 58(2):312-314
  146. Identification of novel biomarkers for Parkinson's disease by metabolomic technologies – HATANO T., SAIKI S., OKUZUMI A., MOHNEY R.P., and HATTORI N. – 2015 – J. Neurol. Neurosurg. Psychiatry, doi: 10.1136/jnnp-2014-309676
  147. Ergothioneine protects Streptomyces coelicolor A3(2) from oxidative stresses – NAKAJIMA S., SATOH Y., YANASHIMA K., MATSUI T., and DAIRI T. – 2015 – J. Biosci. Bioeng., doi: 10.1016/j.jbiosc.2015.01.013
  148. 13C-Nuclear magnetic resonance and Raman spectroscopic studies on ionization and mercury complex of ergothioneine – MOTOHASHI N., MORI I., and SUGIURA Y. – 1976 – Chem. Pharm. Bull., 24(8):1737-1741
  149. Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A – ZHAO Q., WANG M., XU D., ZHANG Q., and LIU W. – 2015 – Nature, 518(7537):115-119
  150. Evaluation of the safety of the dietary antioxidant ergothioneine using the bacterial reverse mutation assay – SCHAUSS A.G., VERTESI A., ENDRES J.R., HIRKA G., CLEWELL A., QURESHI I., and PASICS I. – 2010 – Toxicology, 278(1):39-45
  151. The effect of ergothioneine on clastogenic potential and mutagenic activity: genotoxicity evaluation – SCHAUSS A.G., BERES E., VERTESI A., FRANK Z., PASICS I., ENDRES J., ARUOMA O.A., and HIRKA G. – 2011 – Int. J. Toxicol., 30(4):405-409
  152. Reproductive safety evaluation of L-ergothioneine – FORSTER R., SPEZIA F., PAPINEAU D., SABADIE C., ERDELMEIER I., MOUTET M., and YADAN JC. – 2015 – Food Chem. Toxicol., 80:85-91
  153. Improvement of joint range of motion (ROM) and reduction of chronic pain after consumption of an ergothioneine-containing nutritional supplement – BENSON K.F., AGER D.M., LANDES B., ARUOMA O.I., and JENSEN G.S. – 2012 – Prev. Med., 54(Suppl.):S83-S89
  154. The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation – WEIGAND-HELLER A.J., KRIS-ETHERTON P.M., and BEELMAN R.B. – 2012 – Prev. Med., 54(Suppl.):S75-S78
  155. Effect of Shiitake (Lentinus edodes) extract on antioxidant and inflammatory response to prolonged eccentric exercise – ZEMBRON-LACNY, A., GAJEWSKI, M., NACZK, M., and SIATKOWSKI, I. – 2013 – J. Physiol. Pharmacol., 64(2):249-254
  156. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage – AMES B.N. – 2006 – PNAS, 103(47):17589-17594
  157. Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake – AMES B.N. – 2010 – J. Nucleic Acids, 2010:Article ID 725071
  158. Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging – McCANN J.C., and AMES B.N. – 2011 – Faseb J., 25(6):1793–1814
  159. Redefining oxidative stress – JONES D.P. – 2006 – Antiox. Red. Signal., 8(9):1865-1879
  160. Cysteine as a sustainable sulfur reagent for the protecting-group-free synthesis of sulfur-containing amino acids: biomimetic synthesis of L-ergothioneine in water – ERDELMEIER I., DAUNAY S., LEBEL R., FARESCOUR L. and YADAN J.C. – 2012 – Green Chem., 14(8):2256-2265