The vitamin E reduces liver lipoperoxidation and fibrosis in a model of nonalcoholic steatohepatitis

Abstract

-Context -No effective treatment is available for nonalcoholic steatohepatitis in nowadays. Objectives -To develop a model of nonalcoholic steatohepatitis induced by a methionine and choline deficient diet, as well as to evaluate the role of metformin, vitamin E and simvastatin in the nonalcoholic steatohepatitis progression. Methods -The study analyzed prospectively 50 Wistar rats for a 90-day period and divided them into five groups of 10 rats. One group was given standard rat diet and the others received the methionine and choline deficient diet. Among the four groups that received this diet, one received saline 0,9% and the others received metformin, vitamin E or simvastatin. After the study period, the animals were sacrificed and their blood was collected for biochemical analysis. The livers were removed for lipoperoxidation analysis and for the histological examinations. Results -The methionine and choline deficient diet was able to induce steatosis in 100% of the animals and nonalcoholic steatohepatitis in 27 (69.2%). The alanine aminotransferase levels were significantly higher in the simvastatin group. The aspartate aminotransferase levels were also higher in the simvastatin group, but were statistically significant only in relation to the standard diet group. When lipoperoxidation values were compared, the groups that received standard rat diet and methionine and choline deficient with vitamin E presented significantly lower rates than the others. The presence of fibrosis was significantly smaller in the group receiving vitamin E. Conclusions -The diet used was able to induce steatosis and nonalcoholic steatohepatitis. Besides vitamin E showed to reduce the liver oxidative stress, as well as the fibrosis development. HEADINGS -Vitamin E. Fatty liver. Rats.

Simvastatin Ameliorates Liver Fibrosis via Mediating Nitric Oxide Synthase in Rats with Non-Alcoholic Steatohepatitis-Related Liver Fibrosis

“…The results may be influenced by different study subjects. Zamin Jr I et al observed that simvastatin could elevate the levels of ALT and AST [32]. In their study, Wistar rats, the same as ours, were used to establish the NAFLD models.…”

“…Recent studies mostly demonstrated that simvastatin not only reduced circulating low-density lipoprotein cholesterol but decreased hepatic lipid deposition in patients with NASH. However, it was still controversial whether it improved hepatic inflammation and fibrosis [5,19,32]. Nelson A et al considered that monotherapy with simvastatin does not seem to be an effective treatment for NASH [5].…”

Effects of ovariectomy and resistance training on oxidative stress markers in the rat liver

“…Moreover, several studies have clearly shown that serum levels of vitamin E are significantly reduced in patients with NAFLD (42). Zamin Jr. et al (44) found that vitamin E supplementation significantly reduced OS in the liver and concluded that vitamin E plays an important therapeutic role in preventing diseases such as NASH. In our study, the reduced vitamin E concentrations in both groups of ovariectomized animals (sedentary and trained) can be explained by the low concentration of GSH, which reduces dihydroascorbate into ascorbate and thereby ensures that vitamin E is recycled (Figure 4).…”

Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions

“…This reduced -oxidation capacity can trigger a compensatory increase in activity of hepatic peroxisomal and microsomal fatty acid oxidizing enzymes, like cytochrome P450 2E1 (CYP2E1), that generate large amounts of hydrogen peroxide (20). A key protective function of vitamin E is its strong antioxidant activity that confers defense against reactive oxygen species-mediated lipid peroxidation (21). In addition, there is evidence suggesting that natural vitamin E (RRR--tocopherol and - and -tocopherol) can act as ligand for the pregnane X receptor and activate xenobiotic metabolic pathways (22).…”