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Ameliorative effects of autophagy inducer,simvastatin on alcohol-induced liver disease in a rat model
Authors:Marwa Mohamed Atef  Yasser Mostafa Hafez  Hanan Alsaeed Alshenawy  Marwa Nagy Emam
Affiliation:1. Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt;2. Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt;3. Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt;4. Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
Abstract:
Alcoholic liver disease (ALD) encompasses a variety of liver injuries with various underlying mechanisms but still no effective treatment. So we aimed to monitor the influence of simvastatin on alcohol-induced liver injury and elucidate the underlying mechanisms of its cytoprotective effect. Thirty male albino rats were randomly divided into five equal groups. Group 1 (control): received a standard diet; group 2: received simvastatin (10 mg kg−1 day −1) once a day orally for 8 weeks; group 3: received 20% ethanol (7.9 g kg −1 day −1) daily orally for 8 weeks; group 4: received 20% ethanol along with same simvastatin dose daily for 8 weeks; group 5: received 20% ethanol orally for 8 weeks then received the same simvastatin dose for the next 8 weeks. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Liver tissue malondialdehyde, reduced glutathione levels, and superoxide dismutase activity were estimated. B-cell lymphoma 2 and C/EBP homologous protein levels were evaluated by enzyme linked immunosorbent assay (ELISA). Light chain 3-II and peroxisome proliferation-activated receptor gamma messenger RNA expression was assessed by real-time polymerase chain reaction. Immunohistochemical staining was performed using anti-rat tumor necrosis factor-alpha antibody. Our results revealed that simvastatin treatment was able to ameliorate alcohol-induced liver damage; the improved biochemical data were confirmed by histopathological evaluation. Simvastatin being an autophagy inducer was able to prevent and reverse alcohol-induced liver changes via induction of autophagy, attenuation of oxidative stress, inflammation, and endoplasmic reticulum stress-induced apoptosis. Therefore, our findings suggest that treatment with simvastatin may be a useful approach in the management strategy of ALD.
Keywords:alcoholic liver disease (ALD)  B-cell lymphoma 2 (Bcl-2)  C/EBP homologous protein (CHOP)  light chain 3-II (LC3-II)  peroxisome proliferation-activated receptor gamma (PPARγ)  simvastatin
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