Nicorandil and atorvastatin attenuate carbon tetrachloride – induced liver fibrosis in rats

Abstract

Purpose

The present study aimed to evaluate the possible hepatoprotective effects of nicorandil and atorvastatin against experimentally induced liver fibrosis.

Materials and methods

Wistar male rats wereassigned tofivegroups; control group, fibrosis group, the remaining three groups received in addition to CCl₄, N-acetyl cysteine (300 mg/kg), nicorandil(15 mg/kg) and atorvastatin (20 mg/kg), respectively. Liver fibrosis was induced by intraperitoneal injection of rats with CCl₄ (2 ml/kg), twice weekly for five consecutive weeks. All treatments were administered daily starting from the first day of fibrosis induction for five consecutive weeks. By the end of the experiment, fibrosis biomarkers [hepatic transforming growth factor β1 (TGF-β₁) and hydroxyproline (HYP)], liver function [serum alanine transaminase (ALT), aspartate transaminase (AST), albumin and total bilirubin] were assessed. Moreover, lipid profile [total cholesterol, serum triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)], inflammatory biomarkers [hepatic myeloperoxidase (MPO), serum tumor necrosis factor alpha (TNF-α)], relative liver weight] and oxidative stress biomarkers [malondialdehyde (MDA), glutathione (GSH) and catalase (CAT)] were evaluated. In support, histopathological and immunohistochemical examination of liver alpha smooth muscle actin (α-SMA) were performed.

Results

Nicorandil and atorvastatin effectively reduced fibrosis and liver function biomarkers. They both restored serum lipid profile, TNF-α, MPO, relative liver weight, and hepatic MDA content. Alternatively, they markedly elevated albumin, HDL-C and hepatic content of GSH and CAT. Additionally, a marked histopathological and immunohistochemical improvement of α-SMA was observed.

Conclusion

Nicorandil and atorvastatin might be promising protective agents against liver fibrosis through amelioration of liver function, modulation of fibrous formation, anti-inflammatory and antioxidant potentials.

Keywords:

• Atorvastatin
• carbon tetrachloride
• liver fibrosis
• alpha smooth muscle actin
• Nicorandil
• rats

Acknowledgement

We would like to thank Dr. Kawkab A. Ahmed, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt for her kind help in the immunohistochemical study and Dr. Samraa H. Abdel-Kawi, Lecturer of Histology, Faculty of Medicine, Beni-Suef University, Egypt for her kind help in performing the histopathological study.

Disclosure statement

No potential conflict of interest was reported by the author(s).