Abstract
Carbon tetrachloride (CCl4: 4 ml/kg body weight as a 1:1 mixture of CCl4 and mineral oil) was orally administered to rats. After 12 h the activity of plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) was significantly higher than that of the control group and plasma AST and ALT activities increased thereafter. These results indicated that the necrotic process was active at about 12 h and developed thereafter. After 2–24 h of CCl4 administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced as early as 2 h after CCl4 intoxication and thereafter. Phosphorylated JNK (c-Jun NH2-terminal kinase) and phospho-ERK1/2 (extracellular signal-regulated kinase1/2) were significantly increased transiently 1–3 h after treatment with CCl4, while phosphorylated p38 decreased significantly 1–24 h after CCl4 treatment. These results indicated that the change in MAPKs (mitogen activated protein kinases) slightly preceded that in vitamin C, the most sensitive chemical indicator of oxidative stress.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bruckner JV, Warren DA (2001) Toxic effect of solvents and vapors. In: Klaassen CD (ed) Casarett & Doull’s Toxicology. The basic science of poisons, 6th edn. McGraw-Hill, New York, pp 869–916
Czaja MJ, Liu H, Wang Y (2003) Oxidant-induced hepatocyte injury from menadione is regulated by ERK and AP-1 signaling. Hepatology 37:1405–1413
Gardner AM, Johnson GJ (1996) Fibroblast growth factor-2 suppression of tumor necrosis factor α-mediated apoptosis requires Ras and the activation of mitogen-activated protein kinase. J Biol Chem 271:14560–14566
Ikeda K, Toda M, Tanaka K, Tokumaru S, Kojo S (1998) Increase of lipid hydroperoxides in liver mitochondria and inhibition of cytochrome oxidase by carbon tetrachloride intoxication in rats. Free Radic Res 28:403–410
Kishida E, Nishimoto Y, Kojo S (1992) Specific determination of ascorbic acid with chemical derivatization and high-performance liquid chromatography. Anal Chem 64:1505–1507
Kobayashi M, Takeyoshi I, Yoshinari D, Matsumoto K, Morishita Y (2002) P38 mitogen-activated protein kinase inhibition attenuates ischemia-reperfusion injury of the rat liver. Surgery 131:344–349
Kojo S (2004) Vitamin C, basic metabolism and its function as an index of oxidative stress. Curr Med Chem 11:1041–1064
Lowry OH, Rosebrough NJ, Farr AL, Randall J (1951) Protein measurement with Folin phenol reagent. J Biol Chem 19:265–275
Mendelson KG, Contois L-R, Tevosian SG, Davis RJ, Paulson KE (1996) Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver. Proc Natl Acad Sci USA 93:12908–12813
Nishioka H, Kishioka T, Iida C, Fujii K, Ichi I, Kojo S (2006) Activation of mitogen activated protein kinase (MAPK) during D-galactosamine intoxication in the rat liver. Bioorg Med Chem Lett 16:3019–3022
Plaa GL (2000) Chlorinated methanes and liver injury: highlights of the past 50 years. Annu Rev Toxicol 40:43–65
Rosseland CM, Wierod L, Oksvold MP, Werner H, Ostvold AC, Thoresen GH, Paulsen RE, Huitfeldt HS, Skarpen E (2005) Cytoplasmic retention of peroxide-activated ERK provides survival in primary cultures of rat hepatocytes. Hepatology 42:200–207
Shen H-M, Liu Z-g (2006) JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med 40:928–939
Stadheim TA, Kucera GL (1998) Extracellular signal-regulated kinase (ERK) activity is required for TPA-mediated inhibition of drug-induced apoptosis. Biochem Biophys Res Comm 245:266–271
Sumbayev VV, Yasinska IM (2005) Regulation of MAP kinase-dependent apoptotic pathway: implication of reactive oxygen and nitrogen species. Arch Biochem Biophys 436:406–412
Sun F, Hayami S, Ogiri Y, Haruna S, Tanaka K, Yamada Y, Tokumaru S, Kojo S (2000) Evaluation of oxidative stress based on lipid hydroperoxide, vitamin C and vitamin E during apoptosis and necrosis caused by thioacetamide in rat liver. Biochim Biophys Acta 1500:181–185
Sun F, Tsutsui C, Hamagawa E, Ono Y, Ogiri Y, Kojo S (2001) Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver. Biochim Biophys Acta 1535:186–191
Sun F, Hamagawa E, Tsutsui C, Sakaguchi N, Kakuta Y, Tokumaru S, Kojo S (2003) Evaluation of oxidative stress during apoptosis and necrosis caused by D-galactosamine in rat liver. Biochem Pharmacol 65:101–107
Tommasini I, Cerioni L, Guidarelli A, Cantoni O (2005) ERK1/2-dependent regulation of U937 cell survival after exposure to peroxynitrite. Biochem Biophys Res Comm 329:1282–1287
Tran SEF, Holmstroem TH, Ahonen M, Kaehaeri V-M, Eriksson JE (2001) MAPK/ERK overrides the apoptotic signaling from Fas, TNF, and TRAIL receptors. J Biol Chem 276:16484–16490
Wang Y, Schattenberg JM, Rigoli RM, Storz P, Czaja MJ (2004) Hepatocyte resistance to oxidative stress is dependent on protein kinase C-mediated down-regulation of c-Jun/AP-1. J Biol Chem 279:31089–31097
Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Iida, C., Fujii, K., Kishioka, T. et al. Activation of mitogen activated protein kinase (MAPK) during carbon tetrachloride intoxication in the rat liver. Arch Toxicol 81, 489–493 (2007). https://doi.org/10.1007/s00204-007-0181-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-007-0181-x