Ameliorative effects of autophagy inducer, simvastatin on alcohol‐induced liver disease in a rat model

• Published in: Journal of cellular biochemistry 2019-05, Vol.120 (5), p.7679-7688
• Main Authors: Atef, Marwa Mohamed, Hafez, Yasser Mostafa, Alshenawy, Hanan Alsaeed, Emam, Marwa Nagy
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Alcohol; Alcoholic beverages; alcoholic liver disease (ALD); Alcohols; Apoptosis; Aspartate aminotransferase; Attenuation; Autophagy; B‐cell lymphoma 2 (Bcl‐2); C/EBP homologous protein (CHOP); CCAAT/enhancer-binding protein; Cholesterol; Damage assessment; Density; Endoplasmic reticulum; Enzyme-linked immunosorbent assay; Ethanol; Gene expression; Glutathione; Homology; light chain 3‐II (LC3‐II); Liver; Liver diseases; Lymphocytes B; Lymphoma; Malondialdehyde; Oxidative stress; peroxisome proliferation‐activated receptor gamma (PPARγ); Phagocytosis; Polymerase chain reaction; Proteins; Ribonucleic acid; RNA; Simvastatin; Superoxide dismutase; Triglycerides
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28042

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. 1. Alcoholic liver disease is a worldwide public health issue; however, no available treatment is effective up till now. 2. Increasing number of studies has investigated the pleiotropic effects of statins, mainly its autophagy inducer effect. 3. We aimed to monitor the influence of simvastatin on alcohol‐induced liver injury and elucidate the underlying mechanisms of its cytoprotective effect.