Melatonin versus vitamin E as protective treatment against oxidative stress after extra‐hepatic bile duct ligation in rats

Abstract

The aims of the present study were first to compare the effects of melatonin and vitamin E on the cholestasis syndrome and their protective effect on liver injury, and second, to evaluate the activity of antioxidant enzymes after treatment with these antioxidant drugs. Cholestasis was achieved in adult male Wistar rats by double ligature and section of the extra-hepatic biliary duct. Hepatic and plasma oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and reduced glutathione (GSH) in plasma and homogenates of hepatic tissue. Serum bilirubin, alkaline phosphatase (AP), and gamma-glutamyl-transpeptidase (GGT) were used to evaluate the severity of cholestasis, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Both vitamin E and melatonin were administrated 1 day before and 7 days after bile duct ligation. Acute ligation of the bile duct was accompanied by a significant increased in MDA and a decrease in GSH levels in both plasma and liver, as well as a significant reduction in antioxidant enzymes activities. The overall analysis of both treatments showed that melatonin (500 microg/kg daily) offered significantly better protection against cholestasis and a superior protective effect on hepatic injury than did vitamin E (15 mg/kg daily). Although vitamin E treatment resulted in a reduction of parameters of oxidative stress, the results were significantly better after a much lower daily dose of melatonin. Moreover, melatonin treatment was associated with a significant recovery of antioxidative enzymes. In conclusion, the present paper demonstrates a correlation between the intensity of biliary tract obstruction and increased free radical generation, as well as a direct correlation between the level of oxidative stress and the biochemical markers of liver injury. Melatonin (at a much lower dose than vitamin E) was much more efficient than vitamin E in reducing the negative parameters of cholestasis, the degree of oxidative stress and provided a significantly greater hepatoprotective effect against the liver injury secondary to the acute ligation of the biliary duct.

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

“…It was reported that melatonin can reduce free radical damage by elevating GPx activation [11,39] . Montilla et al [25] reported that acute ligation of the bile duct is accompanied with decreased GSH levels both in plasma and in liver, as well as significantly reduced antioxidant enzyme activities. Treatment with melatonin is associated with a significant recovery of anti-oxidative enzymes such as GPx [25] .…”

“…Montilla et al [25] reported that acute ligation of the bile duct is accompanied with decreased GSH levels both in plasma and in liver, as well as significantly reduced antioxidant enzyme activities. Treatment with melatonin is associated with a significant recovery of anti-oxidative enzymes such as GPx [25] . Tahan et al [12] found that melatonin can restore GPx activity in a rat liver fibrosis model induced by a 14-d dimethylnitrosamine regimen.…”

“…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 the aqueous extract from the root ofPlatycodon grandiflorumon cholestasis-induced hepatic injury in mice

“…Long-standing cholestasis could lead to portal hypertension, hepatic dysfunction, and eventually hepatic cirrhosis (Parola et al, 1996). The pathogenesis is uncertain, but several studies reported that free radicals may play a role in cholestatic liver injury (Montilla et al, 2001;Pastor et al, 1997). Bile acids enhanced the release of free radicals from activated polymorphonuclear and inflammatory cells in cholestatic liver lesions (Dahm et al, 1988).…”

The protective effect of Nigella sativa oil in the brain of the biliary obstructed rats

“…Hepatic fibrosis, the main complication of chronic liver disease, is usually initiated by hepatocyte damage, leading to recruitment of inflammatory cells and platelets, activation of Kuppfer cells and subsequent release of cytokines and growth factors (1). It is known that increased concentration of bile acids induce lipid peroxides, probably related to the stimulation of phagocytic activity in the polymorphonuclear leukocytes and inflammatory cells, which are present after biliary tract obstruction and enhance the tissue injury (2,3). Several clinical and experimental studies have shown that oxygen free radicals have a role in the pathogenesis of tissue injury in obstructive jaundice (4)(5)(6)(7).…”