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Ameliorative effects of autophagy inducer, simvastatin on alcohol‐induced liver disease in a rat model
Author(s) -
Atef Marwa Mohamed,
Hafez Yasser Mostafa,
Alshenawy Hanan Alsaeed,
Emam Marwa Nagy
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28042
Subject(s) - simvastatin , malondialdehyde , liver injury , superoxide dismutase , endocrinology , medicine , alcoholic liver disease , pharmacology , oxidative stress , glutathione , chemistry , biochemistry , cirrhosis , enzyme
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.