Characterization of the protective effects of melatonin and related indoles against ?-naphthylisothiocyanate-induced liver injury in rats

Abstract

The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against alpha-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with cholestasis developed within 24 h, as indicated by both serum levels of alanine aminotransferase (SGPT) and aspartic acid aminotransferase (SGOT) activities and serum total bilirubin concentration. The administration of melatonin or 6-hydroxymelatonin (10 mg/kg body weight) to ANIT-injected rats reduced significantly the serum levels of both SGPT and SGOT and the serum total bilirubin concentration. For all hepatic biochemical markers, melatonin was more effective that 6-hydroxymelatonin. By comparison, the administration of N-acetylserotonin (10 mg/kg body weight) to ANIT-injected rats did not reduce the serum levels of either hepatic enzymes or the serum total bilirubin concentration. In ANIT-injected rats, hepatic lipid peroxidation (LPO) was significantly higher than in control animals and this increase was significantly reduced by either melatonin, 6-hydroxymelatonin or N-acetylserotonin. Furthermore, ANIT treatment caused a significant reduction in liver microsomal membrane fluidity and this reduction was completely reversed by the three indoles. The liver from ANIT-injected rats showed several histopathological alterations; above all there was an acute infiltration of polymorphonuclear neutrophils and an increase in the number of apparent apoptotic hepatocytes. The concurrent administration of melatonin reduced the severity of all morphological alterations, specially the neutrophil infiltration and the number of presumed apoptotic cells. On the contrary, the administration of 6-hydroxymelatonin or N-acetylserotonin did not provide any protective effect in terms of the histopathological alterations. These results indicate that melatonin protects against ANIT-induced liver injury with cholestasis in rats, and suggests that this protective effect is likely due to its antioxidant properties and above all to its capacity to inhibit liver neutrophil infiltration, a critical factor in the pathogenesis of ANIT-induced liver injury. 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration. Finally, N-acetylserotonin in the experimental conditions of this study, only exhibited some antioxidant protection but had no protective effect against ANIT-induced hepatic damage.

Changes in selected biochemical blood parameters in dairy cows after administration of melatonin

“…In previous investigations conducted by the authors of this study (Darul and Kruczyńska, 2004a,b) no effect of melatonin was observed on the activity of liver enzymes. In contrast, Calvo et al (2001) and Montilla et al (2001) reported a reduction in the enzyme activity in rats with hepatopathy after the injection of the hormone.…”

Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats

“…Melatonin also has been reported to stimulate the activities of enzymes and increase gene expression that improves the total antioxidative defense capacity of the organism such as SOD, GSH-Px, and GSH (Kotler et al, 1998). Recent studies indicate that MEL is effective on inhibiting oxidative and kidney and liver damage (Calvo et al, 2001). Melatonin also could dose-dependently reduce kidney lipid peroxide content in CCl 4 -treated rats.…”

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).…”