Nicorandil and mesenchymal stromal cells attenuate amiodarone-induced liver fibrosis in experimental rats

Introduction: Hepatic injury is a known side effect of the antiarrhythmic drug amiodarone. The research aimed to assess the possible protective effects of nicorandil and bone marrow-derived mesenchymal stromal cells (MSCs) in amiodarone-induced liver injury. Methods: Thirty-six male adult albino rats were divided into the following six groups: 1) normal control; 2) nicorandil group (which received oral nicorandil at 10 mg/kg/day); 3) bone marrow mesenchymal stromal cells (BM-MSCs) group (which received 3×10⁶ cells/ml of BM-MSCs suspended in 0.2 ml of phosphate buffered saline (PBS) administered via tail vein injection); 4) amiodarone-induced liver toxicity group (which received oral amiodarone at 25 mg/kg/day once daily); 5) nicorandil-treated group (which received both amiodarone and nicorandil); and 6) MSCs-treated group (which received both amiodarone and BM-MSCs). The fibrotic biomarker transforming growth factor beta-1 (TGF-β1), as well as the inflammatory biomarkers interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), were assessed by quantitative polymerase chain reaction (qPCR). The oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed by enzyme-linked immunosorbent assay (ELISA). Liver function tests, including aspartate transaminase (AST), alanine transaminase (ALT), and albumin, were assessed using colorimetric methods. In support of these analyses, histopathological examination utilizing hematoxylin and eosin (H&E) and Masson's trichrome stains was performed. Results: Nicorandil and MSCs efficiently reduced hepatic fibrosis and improved liver function biomarkers. Serum TNF-α, IL-6, TGF-β1, and MDA values were restored to nearly normal levels. Conclusion: Nicorandil and MSCs are promising hepatoprotective agents against amiodarone-induced hepatic toxicity through their antioxidant and anti-inflammatory potentials.