Melatonin exerts a therapeutic effect on cholestatic liver injury in rats with bile duct ligation

Abstract

: We examined whether melatonin exerts a therapeutic effect on cholestatic liver injury in rats treated with bile duct ligation (BDL). Cholestatic liver injury was induced in male Wistar rats aged 4 wk by ligating the bile duct. Cholestatic liver injury developed 5 days after BDL and continued to 13 days, judging from the levels of serum hepatobiliary injury markers. The serum concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and the hepatic level of TBARS and the activity of hepatic myeloperoxidase, an index of tissue neutrophil infiltration, increased 5 days after BDL, and these increases were enhanced at 13 days. A similar increase in the serum total cholesterol concentration occurred 5 and 13 days after BDL, while the hepatic cholesterol concentration tended to increase at 13 days. When melatonin [10 or 100 mg/kg body weight (BW)] was orally administered to BDL‐treated rats everyday for 8 days, starting 5 days after BDL, the indoleamine attenuated cholestatic liver injury observed at 13 days after BDL was more effective at the higher dose than at the lower dose. The administered melatonin (10 or 100 mg/kg BW) reduced the increases in serum and hepatic TBARS concentrations and hepatic myeloperoxidase activity observed at 13 days after BDL and the higher dose of indoleamine was more effective than the lower dose. Neither dose of melatonin affected the increased serum total cholesterol concentration or the hepatic cholesterol concentration observed at 13 days after BDL. These results indicate that orally administered melatonin at pharmacological doses exerts a therapeutic effect on cholestatic liver injury in rats with BDL possibly through its antioxidant and anti‐inflammatory actions.

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

“…It has been found that melatonin has a higher antioxidant efficiency than vitamin E and GSH, which are known as powerful antioxidants [10] . The antioxidant properties of melatonin prevent acute liver injury induced by ischemiareperfusion [23] , irradiation [24] , bile duct ligation [25][26][27] , and toxins [18,28,29] . Several lines of evidence suggest that melatonin plays an important role in regulation of collagen levels and inhibition of collagen accumulation.…”

Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats

“…It seems likely that the detergent action of bile salts is responsible for solubilization of plasma membranes and cell death, which in turn may lead to oxidative stress, oxidation of reduced glutathione (GSH), and lipid peroxidation [6] . There is growing evidence suggesting that considerable impairment of oxidative stress regulation may play an important role in cholestatic liver injury [7][8][9][10][11] . Acute bile-duct obstruction is characterized by increased lipid peroxidation and by marked decline in reduced GSH, a major cellular antioxidant [12] .…”

Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile duct ligation: role of protein kinase C

“…Thus, our data further provide clinical evidence for the extended usefulness of melatonin in the future. A previous study demonstrated that melatonin reduced the increased serum total bile acid concentration, one of the indexes of cholestasis, in BDL-treated adult rats (25). Given that bile acids are implicated in the pathogenesis of cholestatic liver damage through oxidative stress (26), further studies are warranted to determine whether melatonin can reduce bile acids to regulate PKC-dependent oxidative stress.…”