Abstract
Taurine (2-aminoethylsulfonic acid) has many physiological and pharmacological functions in most tissues. It is abundantly maintained in the liver by both endogenous biosynthesis and exogenous transport, but is decreased in liver diseases. In the hepatic lobule, there are heterogeneous differences in metabolism between the pericentral (PC) and periportal regions, and the distributions of the biosynthesis capacity and specific taurine transporter expression are predominantly in the PC region. In cases of depletion of hepatic taurine level, serious liver damages were observed in the PC region. Taurine has protective effects against xenobiotics-induced liver damages in the PC region, but not xenobiotics-induced PP region damages. The xenobiotics that injure the PC region are mainly catabolized by NADPH-dependent cytochrome P450 2E1 that is also predominantly expressed in the PC region. Taurine treatment seems to be a useful agent for CYP2E1-related liver diseases with predominant damages in the PC region.
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References
Acharya M, Lau-Cam CA (2010) Comparison of the protective actions of N-acetylcysteine, hypotaurine and taurine against acetaminophen-induced hepatotoxicity in the rat. J Biomed Sci 17(Suppl 1):S35
Ariosto F, Riggio O, Cantafora A, Colucci S, Gaudio E, Mechelli C, Merli M, Seri S, Capocaccia L (1989) Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. Eur Surg Res 21:280–286
Awapara J (1956) The taurine concentration of organs from fed and fasted rats. J Biol Chem 218:571–576
Balkan J, Dogru-Abbasoglu S, Kanbagli O, Cevikbas U, Aykac-Toker G, Uysal M (2001) Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress. Hum Exp Toxicol 20:251–254
Balkan J, Kanbagli O, Aykac-Toker G, Uysal M (2002) Taurine treatment reduces hepatic lipids and oxidative stress in chronically ethanol-treated rats. Biol Pharm Bull 25:1231–1233
Bella DL, Hahn C, Stipanuk MH (1999a) Effects of nonsulfur and sulfur amino acids on the regulation of hepatic enzymes of cysteine metabolism. Am J Physiol 277:E144–E153
Bella DL, Hirschberger LL, Hosokawa Y, Stipanuk MH (1999b) Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo. Am J Physiol 276:E326–E335
Bieche I, Narjoz C, Asselah T, Vacher S, Marcellin P, Lidereau R, Beaune P, de Waziers I (2007) Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet Genomics 17:731–742
Bleich S, Degner D (2000) Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats. Alcohol Alcohol 35:215
Buhler R, Lindros KO, Nordling A, Johansson I, Ingelman-Sundberg M (1992) Zonation of cytochrome P450 isozyme expression and induction in rat liver. Eur J Biochem 204:407–412
Butterworth RF (1996) Taurine in hepatic encephalopathy. Adv Exp Med Biol 403:601–606
Chen YX, Zhang XR, Xie WF, Li S (2004) Effects of taurine on proliferation and apoptosis of hepatic stellate cells in vitro. Hepatobiliary Pancreat Dis Int 3:106–109
Chen SW, Chen YX, Shi J, Lin Y, Xie WF (2006) The restorative effect of taurine on experimental nonalcoholic steatohepatitis. Dig Dis Sci 51:2225–2234
Chen X, Sebastian BM, Tang H, McMullen MM, Axhemi A, Jacobsen DW, Nagy LE (2009) Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats. Hepatology 49:1554–1562
Chilakapati J, Shankar K, Korrapati MC, Hill RA, Mehendale HM (2005) Saturation toxicokinetics of thioacetamide: role in initiation of liver injury. Drug Metab Dispos 33:1877–1885
Danielsson H (1963) Present status of research on catabolism and excretion of cholesterol. Adv Lipid Res 1:335–385
Das J, Ghosh J, Manna P, Sil PC (2010a) Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res 44:340–355
Das J, Ghosh J, Manna P, Sil PC (2010b) Taurine protects acetaminophen-induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation. Toxicology 269:24–34
Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845
De La Rosa J, Stipanuk MH (1985) Evidence for a rate-limiting role of cysteinesulfinate decarboxylase activity in taurine biosynthesis in vivo. Comp Biochem Physiol B 81:565–571
Delaney J, Timbrell JA (1995) Role of cytochrome P450 in hydrazine toxicity in isolated hepatocytes in vitro. Xenobiotica 25:1399–1410
Dinçer S, Özenirler S, Öz E, Akyol G, Özogul C (2002) The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage—a light and electron microscopic study. Amino Acids 22:417–426
Dogru-Abbasoglu S, Kanbagli O, Balkan J, Cevikbas U, Aykac-Toker G, Uysal M (2001) The protective effect of taurine against thioacetamide hepatotoxicity of rats. Hum Exp Toxicol 20:23–27
El-Batch M, Hassan AM, Mahmoud HA (2011) Taurine is more effective than melatonin on cytochrome P450 2E1 and some oxidative stress markers in streptozotocin-induced diabetic rats. J Agric Food Chem 59:4995–5000
Erman F, Balkan J, Çevikbas U, Koçak-Toker N, Uysal M (2004) Betaine or taurine administration prevents fibrosis and lipid peroxidation induced by rat liver by ethanol plus carbon tetrachloride intoxication. Amino Acids 27:199–205
Gebhardt R (1992) Metabolic zonation of the liver: regulation and implications for liver function. Pharmacol Ther 53:275–354
Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, Wei Y, Jiang H, Orlicky DJ, Petersen DR, Pagliassotti MJ, Maclean KN (2011) Experimental evidence for therapeutic potential of taurine in the treatment of non-alcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol 301(6):R1710–R1722
Ghandforoush-Sattari M, Mashayekhi S (2008) Evaluation of taurine as a biomarker of liver damage in paracetamol poisoning. Eur J Pharmacol 581:171–176
Gonzalez FJ (2005) Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res 569:101–110
Guengerich FP, Kim DH, Iwasaki M (1991) Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4:168–179
Hammes TO, Pedroso GL, Hartmann CR, Escobar TD, Fracasso LB, da Rosa DP, Marroni NP, Porawski M, da Silveira TR (2012) The effect of taurine on hepatic steatosis induced by thioacetamide in zebrafish (Danio rerio). Dig Dis Sci 57:675–682
Han X, Budreau AM, Chesney RW (2000) The taurine transporter gene and its role in renal development. Amino Acids 19:499–507
Han X, Patters AB, Jones DP, Zelikovic I, Chesney RW (2006) The taurine transporter: mechanisms of regulation. Acta Physiol (Oxf) 187:61–73
Heller-Stilb B, van Roeyen C, Rascher K, Hartwig HG, Huth A, Seeliger MW, Warskulat U, Haussinger D (2002) Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J 16:231–233
Holecek M, Skalsk H, Mraz J (1999) Plasma amino acid levels after carbon tetrachloride induced acute liver damage. A dose–response and time–response study in rats. Amino Acids 16:1–11
Hosokawa Y, Matsumoto A, Oka J, Itakura H, Yamaguchi K (1990) Isolation and characterization of a cDNA for rat liver cysteine dioxygenase. Biochem Biophys Res Commun 168:473–478
Huxtable RJ (1980) Does taurine have a function? Fed Proc 39:2678–2679
Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163
Ikeda S, Tachikawa M, Akanuma SI, Fujinawa J, Hosoya KI (2012) Involvement of gamma-aminobutyric acid transporter 2 in the hepatic uptake of taurine in rats. Am J Physiol Gastrointest Liver Physiol 303:G291–G297
Ito T, Kimura Y, Uozumi Y, Takai M, Muraoka S, Matsuda T, Ueki K, Yoshiyama M, Ikawa M, Okabe M, Schaffer SW, Fujio Y, Azuma J (2008) Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol 44:927–937
Jacobsen JG, Smith LH (1968) Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev 48:424–491
Jung SA, Chung YH, Park NH, Lee SS, Kim JA, Yang SH, Song IH, Lee YS, Suh DJ, Moon IH (2000) Experimental model of hepatic fibrosis following repeated periportal necrosis induced by allylalcohol. Scand J Gastroenterol 35:969–975
Jungermann K, Katz N (1989) Functional specialization of different hepatocyte populations. Physiol Rev 69:708–764
Kaisaki PJ, Jerkins AA, Goodspeed DC, Steele RD (1995) Cloning and characterization of rat cysteine sulfinic acid decarboxylase. Biochim Biophys Acta 1262:79–82
Kang JS, Wanibuchi H, Morimura K, Wongpoomchai R, Chusiri Y, Gonzalez FJ, Fukushima S (2008) Role of CYP2E1 in thioacetamide-induced mouse hepatotoxicity. Toxicol Appl Pharmacol 228:295–300
Kato J, Ido A, Hasuike S, Uto H, Hori T, Hayashi K, Murakami S, Terano A, Tsubouchi H (2004) Transforming growth factor-beta-induced stimulation of formation of collagen fiber network and anti-fibrotic effect of taurine in an in vitro model of hepatic fibrosis. Hepatol Res 30:34–41
Kerai MD, Waterfield CJ, Kenyon SH, Asker DS, Timbrell JA (1998) Taurine: protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats. Amino Acids 15:53–76
Kerai MD, Waterfield CJ, Kenyon SH, Asker DS, Timbrell JA (1999) Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats. Alcohol Alcohol 34:529–541
Kerai MD, Waterfield CJ, Kenyon SH, Asker DS, Timbrell JA (2001) The effect of taurine depletion by beta-alanine treatment on the susceptibility to ethanol-induced hepatic dysfunction in rats. Alcohol Alcohol 36:29–38
Kiernan F (1833) The anatomy and physiology of the liver. Trans R Soc Lond 123:711–770
Kim SK, Kim YC (2002) Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats. Food Chem Toxicol 40:545–549
Kim SK, Seo JM, Jung YS, Kwak HE, Kim YC (2003) Alterations in hepatic metabolism of sulfur-containing amino acids induced by ethanol in rats. Amino Acids 24:103–110
Konishi M, Ishii H (2007) Role of microsomal enzymes in development of alcoholic liver diseases. J Gastroenterol Hepatol 22(Suppl 1):S7–S10
Lang PA, Warskulat U, Heller-Stilb B, Huang DY, Grenz A, Myssina S, Duszenko M, Lang F, Haussinger D, Vallon V, Wieder T (2003) Blunted apoptosis of erythrocytes from taurine transporter deficient mice. Cell Physiol Biochem 13:337–346
Lee SY, Kim YC (2007) Effect of beta-alanine administration on carbon tetrachloride-induced acute hepatotoxicity. Amino Acids 33:543–546
Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ (1996) Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 271:12063–12067
Lieber CS (1997) Cytochrome P-450 2E1: its physiological and pathological role. Physiol Rev 77:517–544
Liu QR, Lopez CB, Nelson H, Mandiyan S, Nelson N (1992) Cloning and expression of a cDNA encoding the transporter of taurine and beta-alanine in mouse brain. Proc Natl Acad Sci USA 89:12145–12149
Liu QR, Lopez-Corcuera B, Mandiyan S, Nelson H, Nelson N (1993) Molecular characterization of four pharmacologically distinct gamma-aminobutyric acid transporters in mouse brain. J Biol Chem 268:2106–2112
Lu Y, Cederbaum AI (2008) CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 44:723–738
Ludwig J, Viggiano TR, McGill DB, Oh BJ (1980) Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55:434–438
Matsuyama Y, Morita T, Higuchi M, Tsujii T (1983) The effect of taurine administration on patients with acute hepatitis. Prog Clin Biol Res 125:461–468
Matsuzaki Y, Tanaka N, Osuga T (1993) Is taurine effective for treatment of painful muscle cramps in liver cirrhosis? Am J Gastroenterol 88:1466–1467
Mehendale HM, Roth RA, Gandolfi AJ, Klaunig JE, Lemasters JJ, Curtis LR (1994) Novel mechanisms in chemically induced hepatotoxicity. FASEB J 8:1285–1295
Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760
Miyazaki T, Matsuzaki Y, Ikegami T, Miyakawa S, Doy M, Tanaka N, Bouscarel B (2004) The harmful effect of exercise on reducing taurine concentration in the tissues of rats treated with CCl4 administration. J Gastroenterol 39:557–562
Miyazaki T, Karube M, Matsuzaki Y, Ikegami T, Doy M, Tanaka N, Bouscarel B (2005) Taurine inhibits oxidative damage of the liver and prevents hepatic fibrosis in carbon tetrachloride induced liver fibrosis in rats. J Hepatol 43:117–125
Nakamura T, Ogasawara M, Koyama I, Nemoto M, Yoshida T (1993) The protective effect of taurine on the biomembrane against damage produced by oxygen radicals. Biol Pharm Bull 16:970–972
Nakashima T, Taniko T, Kuriyama K (1982) Therapeutic effect of taurine administration on carbon tetrachloride-induced hepatic injury. Jpn J Pharmacol 32:583–589
Neuringer M, Imaki H, Sturman JA, Moretz R, Wisniewski HM (1987) Abnormal visual acuity and retinal morphology in rhesus monkeys fed a taurine-free diet during the first three postnatal months. Adv Exp Med Biol 217:125–134
Nieminen ML, Tuomisto L, Solatunturi E, Eriksson L, Paasonen MK (1988) Taurine in the osmoregulation of the Brattleboro rat. Life Sci 42:2137–2143
Obinata K, Maruyama T, Hayashi M, Watanabe T, Nittono H (1996) Effect of taurine on the fatty liver of children with simple obesity. Adv Exp Med Biol 403:607–613
Ogasawara M, Nakamura T, Koyama I, Nemoto M, Yoshida T (1993) Reactivity of taurine with aldehydes and its physiological role. Chem Pharm Bull (Tokyo) 41:2172–2175
Pacioretty L, Hickman MA, Morris JG, Rogers QR (2001) Kinetics of taurine depletion and repletion in plasma, serum, whole blood and skeletal muscle in cats. Amino Acids 21:417–427
Parildar-Karpuzoglu H, Dogru-Abbasoglu S, Balkan J, Aykac-Toker G, Uysal M (2007) Decreases in taurine levels induced by beta-alanine treatment did not affect the susceptibility of tissues to lipid peroxidation. Amino Acids 32:115–119
Parsons RB, Ramsden DB, Waring RH, Barber PC, Williams AC (1998) Hepatic localisation of rat cysteine dioxygenase. J Hepatol 29:595–602
Pasantes MH, Wright CE, Gaull GE (1985) Taurine protection of lymphoblastoid cells from iron-ascorbate induced damage. Biochem Pharmacol 34:2205–2207
Penttila KE (1990) Role of cysteine and taurine in regulating glutathione synthesis by periportal and perivenous hepatocytes. Biochem J 269:659–664
Perez Tamayo R (1983) Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis? Hepatology 3:112–120
Pushpakiran G, Mahalakshmi K, Anuradha CV (2004) Protective effects of taurine on glutathione and glutathione-dependent enzymes in ethanol-fed rats. Pharmazie 59:869–872
Refik Mas M, Comert B, Oncu K, Vural SA, Akay C, Tasci I, Ozkomur E, Serdar M, Mas N, Alcigir G, Yener N (2004) The effect of taurine treatment on oxidative stress in experimental liver fibrosis. Hepatol Res 28:207–215
Reid WD (1972) Mechanism of allyl alcohol-induced hepatic necrosis. Experientia 28:1058–1061
Reymond I, Sergeant A, Tappaz M (1996) Molecular cloning and sequence analysis of the cDNA encoding rat liver cysteine sulfinate decarboxylase (CSD). Biochim Biophys Acta 1307:152–156
Serafini-Cessi F (1972) Conversion of allyl alcohol into acrolein by rat liver. Biochem J 128:1103–1107
Shaffer JE, Kocsis JJ (1981) Taurine mobilizing effects of beta alanine and other inhibitors of taurine transport. Life Sci 28:2727–2736
Sjovall J (1959) Dietary glycine and taurine on bile acid conjugation in man; bile acids and steroids 75. Proc Soc Exp Biol Med 100:676–678
Slater TF, Cheeseman KH, Ingold KU (1985) Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury. Philos Trans R Soc Lond B Biol Sci 311:633–645
Smith KE, Borden LA, Wang CH, Hartig PR, Branchek TA, Weinshank RL (1992) Cloning and expression of a high affinity taurine transporter from rat brain. Mol Pharmacol 42:563–569
Sohn OS, Ishizaki H, Yang CS, Fiala ES (1991) Metabolism of azoxymethane, methylazoxymethanol and N-nitrosodimethylamine by cytochrome P450IIE1. Carcinogenesis 12:127–131
Sturman JA (1993) Taurine in development. Physiol Rev 73:119–147
Sturman JA, Messing JM (1991) Dietary taurine content and feline reproduction and outcome. J Nutr 121:1195–1203
Tappaz M, Bitoun M, Reymond I, Sergeant A (1999) Characterization of the cDNA coding for rat brain cysteine sulfinate decarboxylase: brain and liver enzymes are identical proteins encoded by two distinct mRNAs. J Neurochem 73:903–912
Uchida S, Kwon HM, Yamauchi A, Preston AS, Marumo F, Handler JS (1992) Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(−)-dependent taurine transporter that is regulated by hypertonicity. Proc Natl Acad Sci USA 89:8230–8234
Vermeulen NP, Bessems JG, Van de Straat R (1992) Molecular aspects of paracetamol-induced hepatotoxicity and its mechanism-based prevention. Drug Metab Rev 24:367–407
Warskulat U, Flogel U, Jacoby C, Hartwig HG, Thewissen M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Haussinger D (2004) Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J 18:577–579
Warskulat U, Borsch E, Reinehr R, Heller-Stilb B, Monnighoff I, Buchczyk D, Donner M, Flogel U, Kappert G, Soboll S, Beer S, Pfeffer K, Marschall HU, Gabrielsen M, Amiry-Moghaddam M, Ottersen OP, Dienes HP, Haussinger D (2006) Chronic liver disease is triggered by taurine transporter knockout in the mouse. FASEB J 20:574–576
Watanabe A, Hobara N, Nagashima H (1985) Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ethanol-loaded rats. Experientia 41:1421–1422
Waterfield CJ, Turton JA, Scales MD, Timbrell JA (1991) Taurine, a possible urinary marker of liver damage: a study of taurine excretion in carbon tetrachloride-treated rats. Arch Toxicol 65:548–555
Waterfield CJ, Turton JA, Scales MD, Timbrell JA (1993) Reduction of liver taurine in rats by beta-alanine treatment increases carbon tetrachloride toxicity. Toxicology 29:7–20
Waters E, Wang JH, Redmond HP, Wu QD, Kay E, Bouchier-Hayes D (2001) Role of taurine in preventing acetaminophen-induced hepatic injury in the rat. Am J Physiol Gastrointest Liver Physiol 280:G1274–G1279
Weltman MD, Farrell GC, Liddle C (1996) Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology 111:1645–1653
Weltman MD, Farrell GC, Hall P, Ingelman-Sundberg M, Liddle C (1998) Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology 27:128–133
Wilson AS, Davis CD, Williams DP, Buckpitt AR, Pirmohamed M, Park BK (1996) Characterisation of the toxic metabolite(s) of naphthalene. Toxicology 114:233–242
Wu C, Kennedy DO, Yano Y, Otani S, Matsui-Yuasa I (1999) Thiols and polyamines in the cytoprotective effect of taurine on carbon tetrachloride-induced hepatotoxicity. J Biochem Mol Toxicol 13:71–76
Wu G, Yang J, Sun C, Luan X, Shi J, Hu J (2009) Effect of taurine on alcoholic liver disease in rats. Amino Acids 643:313–322
Yamamoto S (1994) Oral taurine therapy for painful muscle cramp in liver cirrhosis. Am J Gastroenterol 89:457–458
You JS, Chang KJ (1998) Taurine protects the liver against lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis. Adv Exp Med Biol 442:105–112
Acknowledgments
We thank Taisho Pharmaceutical Co., LTD. (Tokyo, Japan) for an educational grant to our taurine research. We are also grateful for the expert advises from the late Dr. Bernard Bouscarel who was associate professor in the Department of Biochemistry and Molecular Biology of the George Washington University, Washington DC, USA.
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Miyazaki, T., Matsuzaki, Y. Taurine and liver diseases: a focus on the heterogeneous protective properties of taurine. Amino Acids 46, 101–110 (2014). https://doi.org/10.1007/s00726-012-1381-0
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DOI: https://doi.org/10.1007/s00726-012-1381-0