Effects of Antidotes on the Hepato- and Nephrotoxicity of Paracetamol in the Rat
During intoxications with paracetamol hepatic and renal failure may develop, the latter also in the absence of liver damage (Boyer et al., 1971; Prescott et al., 1971; Cobden et al., 1982). Several antidotes are available for the treatment of severe paracetamol poisoning, these include mainly precursors of GSH-synthesis like methionine or N-acetylcysteine (Crome et al,. 1976; Prescott et al., 1977). In animal experiments diethyldithiocarbamate (dithiocarb) was shown to be an effective antidote against paracetamol-induced hepatotoxicity, due to its strong inhibitory influence on microsomal monooxygenases (Strubelt et al., 1974; Siegers et al., 1982). No experimental or clinical data, however, are available proving the efficacy of these antidotes in preventing paracetamol-induced renal damage. Moreover, it is still unclear, whether the metabolic pathways leading to hepatotoxic intermediates of paracetamol are the same for exerting nephrotoxic response.
KeywordsUrea Glutathione Prostaglandin Methionine Indomethacin
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Boyer, T.D. and Rouff, S.L. (1971). Acetaminophen-induced hepatic necrosis and renal failure. J. Am. Med. Assoc.
218, 440–441.CrossRefGoogle Scholar
Brehe, J.E. and Burch, H.B. (1976). Enzymatic assay for glutathione. Anal. Biochem.
74, 189–197.PubMedCrossRefGoogle Scholar
Cobden, I., Record, C.O., Ward, M.K. and Kerr, D.N.S. (1982) . Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Br. Med. J.
284, 21–22.CrossRefGoogle Scholar
Crome, P., Vale, J. A. , Volans, G. N. , Widdup, B. and Goulding, R. (1976). Oral methionine in the treatment of severe paracetamol (acetaminophen) overdose. Lancet
2, 829–830.PubMedCrossRefGoogle Scholar
Prescott, L.F., Wright, N., Roscoe, P. and Brown, S.S. (1971). Plasma-paracetamol half-life and hepatic necrosis in patients with paracetamol overdose. Lancet
, 1, 519–522.PubMedCrossRefGoogle Scholar
Prescott, L.F., Park, J., Ballantyne, A., Adriaenssens, P. and Proudfoot, A.T. (1977). Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet
2, 432–434.PubMedCrossRefGoogle Scholar
Sedlack, J. and Lindsay, R.H. (1968). Estimation of total protein-bound and non protein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem.
25, 192–205.CrossRefGoogle Scholar
Siegers, C.-P., Larseille, J. and Younes, M. (1982). Effects of dithiocarb and (+) -catechin on microsomal enzyme activities of rat liver. Res. Commun. Chem. Pathol. Pharmacol.
36, 61–73.PubMedCrossRefGoogle Scholar
Strubelt, O., Siegers, C.-P. and Schutt, A. (1974). The curative effects of cysteamine, cysteine and dithiocarb in experimental paracetamol poisoning, Arch. Toxicol.
33, 55–64.PubMedGoogle Scholar
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