Ameliorative effect of nicorandil on high fat diet induced non-alcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) is an accumulation of excessive amounts of fats in the liver that is not caused by alcohol consumption. It is considered as the most common liver disease in Western societies. The aim of this study is to investigate the possible protective effects of nicorandil and pioglitazone, the benefits of their combination and the possible mechanism underlie these effects in NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. In the next eight weeks, rats were fed the HFD along with pioglitazone (4 mg/kg) or nicorandil in two dose levels (3 or 15 mg/kg), alone or in combination. Chronic HFD administration resulted in significant elevations in serum levels of liver enzymes, total cholesterol, triglycerides, glucose, insulin and HOMA-IR index as compared with the control group. This was coupled with significant increments in liver triglycerides, MDA content and TNF-α as well as a significant reduction in liver GSH content. In comparison with the control group; liver expression of NF-κB was significantly elevated while liver eNOS expression and nitric oxide content were significantly decreased in HFD group. Treatment with pioglitazone or nicorandil either alone or in combination successfully ameliorated the deleterious effects of HFD on the all previous parameters. In conclusion, this investigation indicates a novel role of nicorandil in rats with NAFLD. This effect is mediated through, nitric oxide donor, antioxidant and anti-inflammatory properties, leading to improvement of insulin resistance. It is worth mentioning that the combinations were more effective than the individual drugs.

Elshazly SM 《-》

Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

Zaitone S ，Hassan N ，El-Orabi N ，El-Awady el-S ... -  《-》

Combined treatments with metformin and phosphodiesterase inhibitors alleviate nonalcoholic fatty liver disease in high-fat diet fed rats: a comparative study.

Heeba GH ，El-Deen RM ，Abdel-Latif RG ，Khalifa MMA ... -  《-》

Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure.

Zaitone SA ，Barakat BM ，Bilasy SE ，Fawzy MS ，Abdelaziz EZ ，Farag NE ... -  《-》

Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats.

Akaslan SB ，Degertekin CK ，Yilmaz G ，Cakir N ，Arslan M ，Toruner FB ... -  《-》