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.