Preventive effect of melatonin on the progression of α‐naphthylisothiocyanate‐induced acute liver injury in rats

Abstract

: The preventive effect of melatonin on the progression of α‐naphthylisothiocyanate (ANIT)‐induced acute liver injury with cholestasis was examined in rats treated once with the hepatotoxin [75 mg/kg body weight (BW), i.p.]. In rats treated with ANIT alone, liver injury with cholestasis occurred 24 hr after treatment and progressed at 48 hr, judging from the serum levels of hepatobiliary marker enzymes and components. Melatonin (10 or 100 mg/kg BW) was orally administered to the ANIT‐treated rats, 24 hr after the hepatotoxin treatment at which time hepatic injury had already developed. The administered indoleamine prevented the progression of liver cell damage rather than biliary cell damage more effectively at the higher dose than at the lower dose. In rats treated with ANIT alone, the serum and hepatic concentrations of thiobarbituric acid reactive substances, an index of lipid peroxidation, and the hepatic activity of myeloperoxidase, an index of tissue neutrophil infiltration, increased 24 hr after treatment and further increased at 48 hr. In the liver of rats treated with ANIT alone, Cu,Zn‐superoxide dismutase activity decreased 24 hr after treatment and was further reduced at 48 hr, although there was no change in Mn‐superoxide dismutase activity. Catalase and Se‐glutathione peroxidase activities also decreased at 48 hr, while reduced glutathione concentrations remained increased at 24 and 48 hr. The melatonin administered to the ANIT‐treated rats attenuated the increases in serum and hepatic concentrations of thiobarbituric acid reactive substances and the decreases in hepatic activities of Cu,Zn‐superoxide dismutase, catalase, and Se‐glutathione peroxidase found at 48 hr after the hepatotoxin treatment more effectively at the higher dose than at the lower dose; on the other hand, melatonin treatment had no effect on the increases in hepatic myeloperoxidase activity and reduced glutathione concentration found at 48 h. These results indicate that orally administered melatonin at pharmacological doses prevents the progression of ANIT‐induced acute liver injury, mainly liver cell damage, in rats, and suggest that the administered melatonin exerts these preventive effects through its direct and indirect antioxidant actions.

Resveratrol effectively attenuates α-naphthyl-isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms

“…In the present study, an enhancement in the hepatic activity of MPO, an index of tissue neutrophil infiltration, occurred after ANITinduced liver injury. These data confirm previously reported results [30,31] . Resveratrol administered intraperitoneally to ANIT-treated rats after the appearance of liver injury significantly reduced the increase in hepatic MPO activity.…”

Protective effect of Danning tablet on acute livery injury with cholestasis induced by α-naphthylisothiocyanate in rats

“…Lipid peroxidation which can be monitored by measuring the level of liver MDA (Ohkawa et al, 1979) is regarded as one of the basic mechanisms of tissue damage caused by free radicals (Esterbauer et al, 1991). It has been suggested that liver LPO content increases before the formation of liver injury and further increases with the formation and progression of the injury in rats intoxicated once with ANIT Kongo et al, 1999;Calvo et al, 2001;Ohta et al, 2003). The antioxidant enzymes such as SOD, CAT and GPx are the first line of defense against superoxide anion free radicals and hydrogen peroxide mediated injury (Gutteridge et al, 1979;Beck and Levander, 1998).…”

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

“…In the present study melatonin administered in the morning improved the GSH status in the liver of benzene-treated rats. There are reports that pharmacological doses of melatonin given orally to alpha-naphthylisothiocyanate-and N-acetyl-para-aminophenol (APAP)-treated rats did not affect GSH levels in acute liver injury (15,16). In contrast, other reports indicate benefi cial effects of melatonin on arsenic-induced oxidative stress in the liver and kidney of Wistar rats (18).…”

“…It was found to protect against the toxicity of alpha-naphthylisothiocyanate (15), acetaminophen (16), irradiation (17), and arsenic (18). In addition to liver, benefi cial effects of melatonin have been observed in the skin (19), cerebral ischaemia (20), and ocular diseases (21).…”