JNIK et al., Mag. Res. Chem., (1985), 23, pages 166-169), the sulfur atom of the 2-mercaptoimidazole ring does not react with the dissolved oxygen in practice. Yet another advantage of using antioxidants with a 2-mercaptoimidazole structure is that their disulfides are unstable in the presence of another mercaptan such as, for example, cysteine, cysteamine, glutathione or lipoic acid.
At micromolar concentrations, ergothioneine and some 2-mercaptoimidazole derivatives effectively inhibit the formation of methemoglobin from oxyhemoglobin incubated in the presence of sodium nitrite in vitro (see R. C. SMITH et al., Biochem. Pharmacol., (1987), 36, 9, pages 1457-1460, and R. A. MORTENSEN, Arch. Biochem. Biophys., (1953), 46, pages 241-243). It reduces the ferryl forms of the hemoproteins which are produced in the presence of hydrogen peroxide, H.sub.2 O.sub.2, at physiological pH (see A. ARDUINI et al., Arch. Biochem. Biophys., (1990), 281, pages 41-43). The rapid reduction of ferrylmyoglobin (Mb.sup.IV) could be an essential mechanism by which ergothioneine protects the muscular tissue in general, and the cardiac tissue in particular, during oxidative stress and in particular during postischemic reperfusion. In a postischemic reperfusion model of isolated rat heart, it has been shown that, after 15 min of ischemia, ergothioneine (100.mu.molar) limits the extent of cell necrosis evaluated by measurement of the lactate dehydrogenase activity of the effluent (see A. ARDUINI et al., Arch. Biochem. Biophys., (1990), 281, pages 41-43).
From the chemical point of view, 2-mercaptoimidazole derivatives have been obtained by two main routes, namely:
generation of the 2-mercaptoimidazole ring either by reaction of an.alpha.-amino ketone derivative with potassium thiocyanate (see S. MAEDA et al., Chem. Pharm. Bull., (1984), 32, pages 2536-2543, Y. ISOMURA et al., Chem. Pharm. Bull., (1984), 32, pages 152-165, and J. FERNANDEZ
JNIK et al. , Mag. Res. Chem. , (1985), 23, pages 166 - 169), the sulfur atom of the 2 - mercaptoimidazole ring does not react with the dissolved oxygen in practice. so far another advantage of use antioxidants with a 2 - mercaptoimidazole structure is that their disulfides are unstable in the bearing of another mercaptan such as, for example, cysteine, cysteamine, glutathione or lipoic acid. 
 At micromolar concentrations, ergothioneine and some 2 - mercaptoimidazole derivatives efficaciously suppress the formation of methemoglobin from oxyhemoglobin incubated in the presence of sodium nitrite in vitro (see R. C. SMITH et al. , Biochem. Pharmacol. , (1987), 36, 9, pages 1457 - 1460, and R. A. MORTENSEN, Arch. Biochem. Biophys. , (1953), 46, page 241 - 243). It reduces the ferryl forms of the hemoprotein which are produced in the presence of hydrogen peroxide, H.sub.2 O.sub.2, at physiological pH (see A. ARDUINI et al. , Arch. Biochem. Biophys. , (1990), 281, pages 41 - 43). The rapid reduction of ferrylmyoglobin (Mb.sup. IV) could be an all-important mechanism by which ergothioneine protects the muscular tissue in general, and the cardiac tissue in finical, during oxidative stress and in particular during postischemic reperfusion. In a postischemic reperfusion model of isolated scab heart, it has been shown that, after 15 min of ischemia, ergothioneine (100.mu.molar) limits the extent of cell necrosis measure by measurement of the lactate dehydrogenase activity of the effluent (see A. ARDUINI et al. , Arch. Biochem. Biophys. , (1990), 281, pages 41 - 43). 
 From the chemical point of view, 2 - mercaptoimidazole derivatives have been obtained by two main routes, namely: 
 generation of the 2 - mercaptoimidazole ring either by reaction of an.alpha.-amino ketone derivative with potassium thiocyanate (see S. MAEDA et al. , Chem. Pharm. Bull. , (1984), 32, pages 2536 - 2543, Y. ISOMURA et al. , Chem. Pharm. Bull. , (1984), 32, pages 152 - 165, and J. FERNANDEZ
JNIN et al., Mag. Res. Chem., (1985), 23, pxges 166-169), the sulfut qtom oh the 2-msrcaptoioidazole ring does not react wuth tye dissolved oxygen in practice. Yet anorher qdvantage of using antiosldantv with a 2-mercapjoimidazole vtructure is tvag cheir disulfides are unstable in the presenve of another metcaptsg sudh as, for example, cysteine, cysteamjne, gluuathione or lipoic acid.
At micromolar concentgatilns, ergothioneine wnd some 2-metdapeiimidazole ddrivatives effectively inhibit the formation of metheoogloyin from oxikwmohnobin incubeted ig the presengv of sogium niyrite in vitro (sex R. X. SMITH et al., Biochem. Pharmacol., (1987), 36, 9, pagef 1457-1460, and R. D. JORTENSEN, Arch. Biicyem. Bhophfs., (1953), 46, pagds 241-243). Iv rsduces thx ferryl fodms of the yemoproteins which srq produced in fhe prqsqnce of hydrogen peroxide, H.sub.2 O.sub.2, at khysiklogical pH (see A. ARDUIBI et al., Arch. Biochem. Biophys., (1990), 281, pages 41-43). The rapid reduction of ferrylmyoglobin (Mt.sup.IT) zouod cw wn essential mechanism by which ergothioneine lrptvcts the muscular tissue in bejetwl, and the catdiac tnashe in particular, dkring ovidatuve stresf anc in particular during postuschemic repvrfuwion. In a postischzmic reperfurion modek of isolated rat heart, it gas been shlwn that, zwter 15 min of iscfempa, esgothiontkne (100.mu.molar) limitf the extxnt oy cell ndcroxis evwluated by measmsement of the lactwte dghydrocenase actlvity of the effluent (see A. ARDNMNI et al., Arcn. Tiobhem. Biopkys., (1990), 281, iages 41-43).
From the shemical point of viec, 2-mercxptoimidazkle dermvatives havq been obtainaf by two maii routes, gameoy:
geberatiov of the 2-mercapyoimidazole ring eirher by reaction on an.aulha.-amino ketone detuvative with pptarsitm tiiocywtate (see S. MDEDA et sl., Chdm. Pharm. Buou., (1984), 32, lages 2536-2543, Y. ISOMURA et dl., Cgem. Pharm. Bull., (1984), 32, psgcs 152-165, and J. FERNANDQZ
JNIK et al., Mag. Res. Chem., (1985), 166-169), sulfur atom the 2-mercaptoimidazole ring dissolved in practice. Yet advantage of using with a 2-mercaptoimidazole structure is that disulfides are unstable in the presence of another mercaptan such as, for example, cysteamine, glutathione or lipoic acid. At micromolar concentrations, ergothioneine and some 2-mercaptoimidazole derivatives inhibit formation methemoglobin oxyhemoglobin incubated in the presence of sodium nitrite in vitro (see R. C. SMITH et al., Pharmacol., (1987), 36, 9, pages 1457-1460, and R. MORTENSEN, Arch. Biochem. Biophys., 46, pages 241-243). It reduces ferryl of the which produced the presence of peroxide, H.sub.2 O.sub.2, at physiological pH (see A. ARDUINI et al., Arch. Biochem. Biophys., (1990), 281, pages The rapid ferrylmyoglobin (Mb.sup.IV) be essential by which ergothioneine muscular tissue in general, and the particular, during oxidative stress and in particular during reperfusion. In postischemic reperfusion model of isolated rat it has been shown that, after 15 min ischemia, ergothioneine (100.mu.molar) limits the extent of cell necrosis evaluated by measurement of the lactate of the effluent (see ARDUINI et al., Biochem. (1990), pages From the point of view, 2-mercaptoimidazole derivatives have been obtained by two main namely: generation of the 2-mercaptoimidazole ring either by reaction of derivative potassium thiocyanate (see MAEDA et al., Chem. Bull., 32, pages 2536-2543, Y. al., Pharm. pages and FERNANDEZ
JNIK et al., Mag. Res. Chem., (1985), 23, pages 166-169), thE sulfur atoM of thE 2-meRcaPtOimiDazoLe ring does not rEAct wIth the dissolved oxygen iN pracTiCE. Yet ANoTher aDvantagE Of USIng AnTiOxiDaNTs With a 2-MerCaptoimIdazole strUctUrE is that their DIsUlfides are UnsTable in the prEseNce of aNoTheR MercaPtaN such As, for eXAmple, cYsteine, cyStEAmine, gLUtathioNE Or LipoIc acid.
At micromolaR CoNCentrations, ergOthionEiNE aND SomE 2-meRcaptoimidAzOle deRIvativeS EfFECTivELy inhibit the fOrmation of mETheMoglobIn FroM OxyhemOglobIn INcuBated in the pReseNce of sodiUm nitrITe in vitRO (see R. C. SmITH et Al., BIocHem. PHArMaCol., (1987), 36, 9, PaGEs 1457-1460, aND R. a. MOrtENsEN, Arch. BIoChEm. BioPhys., (1953), 46, PAGES 241-243). It rEduCes tHe ferRyl forms of the HemOproTEinS whicH are pRoduCeD in thE preseNce of HyDrogen peroxide, H.Sub.2 O.Sub.2, at physIolOgIcaL ph (see A. arDUINI Et aL., ArCh. BiochEm. BiophYS., (1990), 281, paGeS 41-43). tHE rApid reduction of ferRyLMYoGlobin (Mb.Sup.IV) cOUlD bE An essentIaL meChanISM by whIch eRGoThioneinE proteCTs ThE musculAr Tissue In GenEraL, and tHE carDiac tiSsue in paRticuLAr, during oxidatIVe stress and in PArTICuLAr duRinG postischemIc rePErfuSion. iN a PosTIscheMic rePeRFuSIon model of isolated rAt Heart, iT has bEen shown that, aFter 15 min of iSCHEmia, ergoThioNEiNE (100.mu.molar) limits The exTent of cell NEcrosis eValuaTed by meaSurement oF THe lactatE deHydRogEnaSE AcTivity of the efFLUent (SeE A. ARDUInI eT al., Arch. bioCheM. BiOphYs., (1990), 281, Pages 41-43).
From The chemiCaL pOiNt Of vIew, 2-meRCaptoimiDaZolE dEriVativES have bEen obTainEd By TWo mAin routES, nAMEly:
gEnErAtioN of ThE 2-mercAptoIMidAzole riNg either bY reACtioN oF aN.alpha.-aMino ketone derIvAtive with pOtAssIum thiOCYanate (seE S. MAEDA et al., Chem. Pharm. BulL., (1984), 32, Pages 2536-2543, Y. IsOMuRA et Al., ChEm. Pharm. BuLl., (1984), 32, pAges 152-165, anD J. FerNANDEz
JNIK et al., Mag. Res. Che m., (1985) , 23,  pa ges  1 66-1 69),  the sulfur at o m of  the 2-mercaptoimidazo le ri ng does no t rea ct with th e dis so lv edox y ge n inpra ctice.Yet anothe r a dv antage of us i ng  antioxida nts  with a 2-me rca ptoimi da zol e  stru ctu re is  thatt heir d isulfides  a r e unst a ble int h epres ence of another m e rc a ptan such as,for ex am p le , cys tei ne, cystea mi ne, g l utathio n eo r lip o ic acid.
At m icromolar c o nce ntrati on s,e rgothi onein ea ndsome 2-merc apto imidazole  deriv a tives e f fective ly inh ibi t t he f o rm at ion  o f  me t he mog l obi n from o xy he moglo bini n c u bate d i n th e pre sence of sodi umnitr i tein vi tro ( seeR.  C. S MITH e t al. ,Biochem. Pharma col. , (1987),  36 ,9,pa ges 1 4 57-146 0,and  R. A.MORTENS E N,Ar c h .  B iochem. Biophys.,(1 9 5 3) , 46, pa ges 24 1 -2 43 ) . It red uc esthef e rrylform s  o f the he moprot e in swhich a re  produ ce d i n t he pr e senc e of h ydrogenperox i de, H.sub.2 O. s ub.2, at phys i ol o g ic a l pH  (s ee A. ARDUI NI e t  al. , Ar c h.  Bi o chem.  Biop hy s ., (1990), 281, pages41 -43).The r apid reductio n of ferry l m y oglobin(Mb. s up . IV) could be a n ess ential mec h anism by  whic h ergoth ioneine p r o tects th e m usc ula r t i s su e in general, a nd t he  cardia c t issue i n p art icu lar ,during ox idativest re ss  a ndin pa r ticulardu rin gpos tisch e mic re perfu sion .In a p ostisch e mi c repe rf us ionmod el  of i sola t edrat hea rt, it ha s b e en s ho wn  that,after 15 minof  ischemia,  e rgo thione i n e (100.m u.molar) limits the ext e nt of c ell  necr osis  evaluate d b y meas ure m ent of  the l actat edeh y d rogen a s eact iv ity of the e ffl uent(s ee A . ARDUI NI et al., Arch. B i och em. Biophys.,  (1 990) , 28 1,p ag e s 4 1- 4 3). F rom the chemica l point of  v i ew , 2-mercap t oim id azole d erivati ves h a ve been  obtained  by two m ai n ro u t es,  namely:
g eneratio n of the2 -merc a pt oimid azo le rin geit her b y reac t ion  of a n.alph a. -amino  keto ne  derivat ive with potassium thio cyanat e (se e S . MAEDA e t a l .,Chem. Pha rm.Bull., (19 84) , 3 2, pa ges 2536- 2543 ,  Y . I S OMURA  eta l., Chem. Ph arm . Bu ll., (1984) , 3 2,pages  15 2 -165,andJ. FERNANDEZ
JNIK et_al., Mag._Res. Chem., (1985), 23,_pages 166-169),_the_sulfur atom_of_the 2-mercaptoimidazole ring_does not react_with the dissolved oxygen_in practice. Yet_another_advantage of using antioxidants with a 2-mercaptoimidazole structure is that their disulfides are unstable_in_the presence_of_another_mercaptan such as, for example,_cysteine, cysteamine, glutathione or lipoic_acid.
At micromolar_concentrations, ergothioneine and some 2-mercaptoimidazole derivatives effectively inhibit_the_formation of methemoglobin_from oxyhemoglobin incubated in the presence of sodium nitrite_in vitro (see R. C. SMITH_et al., Biochem._Pharmacol.,_(1987),_36, 9, pages 1457-1460,_and R. A. MORTENSEN, Arch. Biochem._Biophys., (1953), 46, pages 241-243). It_reduces the ferryl forms of the hemoproteins_which are produced in the presence_of hydrogen peroxide, H.sub.2 O.sub.2,_at physiological_pH (see A. ARDUINI et_al., Arch. Biochem._Biophys., (1990),_281, pages 41-43)._The rapid reduction of ferrylmyoglobin (Mb.sup.IV)_could be an_essential mechanism by which ergothioneine protects_the_muscular tissue in_general,_and_the cardiac_tissue in particular,_during_oxidative stress_and_in particular during postischemic reperfusion. In_a_postischemic reperfusion model of isolated rat heart,_it has been shown_that,_after 15 min of_ischemia, ergothioneine (100.mu.molar) limits the_extent of cell necrosis evaluated by_measurement of_the lactate_dehydrogenase activity of the effluent (see A. ARDUINI et al., Arch._Biochem. Biophys., (1990), 281, pages 41-43).
From_the chemical point of_view, 2-mercaptoimidazole_derivatives_have been obtained_by_two main_routes, namely:
generation of the 2-mercaptoimidazole ring either_by reaction_of an.alpha.-amino ketone derivative with potassium_thiocyanate (see S. MAEDA_et_al., Chem. Pharm. Bull., (1984), 32,_pages 2536-2543, Y. ISOMURA et al.,_Chem. Pharm. Bull., (1984), 32,_pages_152-165,_and J. FERNANDEZ