Aims: Nonalcoholic steatohepatitis (NASH) is a major form of chronic liver disease and is becoming the leading indication for liver transplantation. In addition to being a major contributor to death from liver disease, NASH imposes a substantial econo...
Aims: Nonalcoholic steatohepatitis (NASH) is a major form of chronic liver disease and is becoming the leading indication for liver transplantation. In addition to being a major contributor to death from liver disease, NASH imposes a substantial economic burden on health care systems in developing countries. Vitamin E is a potent antioxidant, anti-inflammatory that has been shown to reduce oxidative stress in diabetic patients. We investigated the effects of Vitamin E in preventing liver fibrosis in a rodent model of NASH.
Methods: Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the Vitamin E group (n=10) received 10 IU/kg/day by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, lipoperoxidation analysis and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1a) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme linked immunosorbent assay (ELISA).
Results: Vitamin E treatment restored mitochondrial function and reduced lipoperoxidation levels, collagen deposition by nearly 76% compared to the NASH group. Vitamin E upregulated PGC1a and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no significant differences in HSP60, HSP90 and GST expression.
Conclusions: Vitamin E modulated PGC1a expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.