Melatonin prevents oxidative stress,inflammatory activity,and DNA damage in cirrhotic rats

BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma.In animals,this can be reproduced by an experimental model of bile duct ligation(BDL).Melatonin(MLT)is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties,including its antioxidant potential.AIM To evaluate MLT’s effects on oxidative stress,the inflammatory process,and DNA damage in an experimental model of secondary biliary cirrhosis.METHODS Male Wistar rats were divided into 4 groups:Control(CO),CO+MLT,BDL,and BDL+MLT.MLT was administered(20 mg/kg)daily beginning on day 15 after biliary obstruction.On day 29 the animals were killed.Blood samples,liver tissue,and bone marrow were collected for further analysis.RESULTS BDL caused changes in biochemical and histological parameters and markers of inflammatory process.Thiobarbituric acid(0.46±0.01)reactive substance levels,superoxide dismutase activity(2.30±0.07)and nitric oxide levels(2.48±0.36)were significantly lower(P<0.001)n the groups that received MLT.DNA damage was also lower(P<0.001)in MLT-treated groups(171.6±32.9)than the BDL-only group(295.5±34.8).Tissue damage and the expression of nuclear factor kappa B,interleukin-1β,Nrf2,NQO1 and Hsp70 were significantly lower in animals treated with MLT(P<0.001).CONCLUSION When administered to rats with BDL-induced secondary biliary cirrhosis,MLT effectively restored the evaluated parameters.

Melatonin restores zinc levels,activates the Keap1/Nrf2 pathway,and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity

BACKGROUND Melatonin(MLT)is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations,due to its action against free radicals.AIM To evaluate the effect of MLT on carbon tetrachloride(CCl_(4))induced liver injury in rats in terms of oxidative stress,reticular stress,and cell damage.METHODS Twenty male Wistar rats(230-250 g)were divided into four groups:Control rats,rats treated with MLT alone,rats treated with CCl_(4)alone,and rats treated with CCl_(4)plus MLT.CCl_(4)was administered as follows:Ten doses every 5 d,ten every 4 d,and seven every 3 d.MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment(16th wk).RESULTS MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl_(4)treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity,with a lower reduction in serum zinc levels,guaranteeing a reduction in liver damage;additionally,it increased the expression of nuclear factor(erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein 1.MLT also decreased the expression of the proteins associated with endoplasmic reticulum stress,i.e.,glucose-regulated protein 78 and activating transcription factor 6,as well as of heat shock factor 1 and heat shock protein 70.CONCLUSION MLT has a hepatoprotective effect in an experimental model of CCl_(4)-induced liver injury,since it reduces oxidative stress,restores zinc levels,and modulates endoplasmic reticulum stress.