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Titolo:
The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats
Autore:
Yamamoto, H; Watanabe, T; Mizuno, H; Endo, K; Fukushige, J; Hosokawa, T; Kazusaka, A; Fujita, S;
Indirizzi:
Hokkaido Univ, Grad Sch Vet Med, Dept Environm Vet Sci, Lab Toxicol,Kita Ku, Sapporo, Hokkaido 0600818, Japan Hokkaido Univ Sapporo Hokkaido Japan 0600818 oro, Hokkaido 0600818, Japan Sankyo Co Ltd, Neurosci & Immunol Res Labs, Med Safety Res Labs, Tokyo 1408710, Japan Sankyo Co Ltd Tokyo Japan 1408710 Safety Res Labs, Tokyo 1408710, Japan
Titolo Testata:
FREE RADICAL RESEARCH
fascicolo: 1, volume: 34, anno: 2001,
pagine: 69 - 80
SICI:
1071-5762(2001)34:1<69:TAEODA>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILSON-DISEASE GENE; LIPID-PEROXIDATION; HEREDITARY HEPATITIS; FULMINANT-HEPATITIS; DIHYDROLIPOIC ACID; HEME OXYGENASE; OXIDANT INJURY; ASCORBIC-ACID; THIOCTIC ACID; LIVER-CANCER;
Keywords:
LEC rats; DL-alpha-lipoic acid (LA); copper (Cu); hepatitis; reactive oxygen species (ROSs);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Fujita, S Hokkaido Univ, Grad Sch Vet Med, Dept Environm Vet Sci, Lab Toxicol,Kita Ku, N18,W9, Sapporo, Hokkaido 0600818, Japan Hokkaido Univ N18,W9 Sapporo Hokkaido Japan 0600818 00818, Japan
Citazione:
H. Yamamoto et al., "The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats", FREE RAD RE, 34(1), 2001, pp. 69-80

Abstract

The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson'sdisease and spontaneously develop acute hepatitis with severe jaundice. Inthis study we examined the protective effect of DL-a-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-l, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it hadno effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded thatLA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

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Documento generato il 23/09/20 alle ore 05:59:11