Time course of collagen peak in bile duct-ligated rats

<p>Abstract</p> <p>Background</p> <p>One of the most useful experimental fibrogenesis models is the "bile duct-ligated rats". Our aim was to investigate the quantitative hepatic collagen content by two different methods during the different stages of hepatic fibrosis in bile duct-ligated rats on a weekly basis. We questioned whether the 1-wk or 4-wk bile duct-ligated model is suitable in animal fibrogenesis trials.</p> <p>Methods</p> <p>Of the 53 male Wistar rats, 8 (Group 0) were used as a healthy control group. Bile duct ligation (BDL) had been performed in the rest. Bile duct-ligated rates were sacrificed 7 days later in group 1 (10 rats), 14 days later in group 2 (9 rats), 21 days later in group 3(9 rats) and 28 days later in group 4 (9 rats). Eight rats underwent sham-operation (Sham). Hepatic collagen measurements as well as serum levels of liver enzymes and function tests were all analysed.</p> <p>Results</p> <p>The peak level of collagen was observed biochemically and histomorphometricly at the end of third week (P < 0.001 and P < 0.05). Suprisingly, collagen levels had decreased with the course of time such as at the end of fourth week (P < 0.01 and P < 0.05).</p> <p>Conclusion</p> <p>We have shown that fibrosis in bile duct-ligated rats is transient, i.e. reverses spontaneously after 3 weeks. This contrasts any situation in patients where hepatic fibrosis is progressive and irreversible as countless studies performed by many investigators in the same animal model.</p

Understanding mechanisms of the pathogenesis of nonalcoholic fatty liver disease

A central issue in the understanding of the pathogenesis of nonalcoholic fatty liver disease is the problem of the underlying mechanisms which are not fully understood. In the setting of excessive central adiposity, insulin resistance is the major underlying cause of fat accumulation in hepatocytes. Because of the difficulties with human trials, several animal models have been developed for this purpose mainly characterized as follows: genetically disturbed or murine fatty liver, methionine-choline deficient diet fed or murine steatohepatitis, and high-fat or sucrose diet fed models. Although these animal models have provided useful information, none of them accurately reflect genetic, metabolic and biochemical characteristics of the human disease

Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats

Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option

Melatonin ameliorates liver fibrosis induced by bile-duct ligation in rats

Background: Hepatic stellate cells, the main mediators in the pathogenesis of fibrosis, are triggered by free radicals and produce collagen. Melatonin is a powerful physiologic scavenger of hydroxyl radicals. It is also involved in the inhibitory regulation of the collagen content in tissue. There is no effective treatment available for liver fibrosis. Our objective was to evaluate the effects of melatonin on liver fibrosis induced by bile-duct ligation (BDL) in rats

Melatonin ameliorates liver fibrosis induced by bile-duct ligation in rats

Background: Hepatic stellate cells, the main mediators in the pathogenesis of fibrosis, are triggered by free radicals and produce collagen. Melatonin is a powerful physiologic scavenger of hydroxyl radicals. It is also involved in the inhibitory regulation of the collagen content in tissue. There is no effective treatment available for liver fibrosis. Our objective was to evaluate the effects of melatonin on liver fibrosis induced by bile-duct ligation (BDL) in rats