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

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.

Autophagy, Metabolism, and Alcohol-Related Liver Disease: Novel Modulators and Functions

“…Consistent with earlier findings that autophagy can protect animals from alcohol-induced liver injury and steatosis, several recent studies confirmed the ameliorative effects of hepatic autophagy in multiple ALD animal models, including an 8-week alcohol-fed rat model [97] and an alcohol-plus-LPS ALD mouse model [98]. Augmenter of liver regeneration (ALR) is a factor that can promote liver growth and it has been shown to protect against acute liver injury from variable insults [99].…”

Effect of Simvastatin on Alcohol Induced Hepatitis in Experimental Rat

“…Meanwhile, upon simvastatin treatment, the treated group showed a statistically significant decrease of liver enzymes indicating its ameliorative effect. The results revealed low ALT and AST levels in the ethanol-treated group with the lowest levels observed in ethanol group that was co-treated with simvastatin [12].…”

Simvastatin alleviated diabetes mellitus‐induced erectile dysfunction in rats by enhancing AMPK pathway‐induced autophagy

“…Gu reported that simvastatin alleviated airway inflammation and remodeling by upregulating autophagy in mouse models of asthma . Atef found that simvastatin, an autophagy inducer, was able to prevent and reverse alcohol‐induced liver changes partly by the induction of autophagy, attenuation of oxidative stress, inflammation, and endoplasmic reticulum stress‐induced apoptosis . Therefore, moderate enhancement of autophagy may be the reason why simvastatin may alleviate corpus cavernosum fibrosis and thus improve erectile function.…”