Drug Design, Development and Therapy (Dec 2018)
Cytoprotective effects of molsidomine against methotrexate-induced hepatotoxicity: an experimental rat study
Abstract
Emine Turkmen Samdanci,1 Mustafa Huz,1 Onural Ozhan,2 Kevser Tanbek,3 Esra Pamukcu,4 Ayse Nur Akatli,1 Hakan Parlakpinar21Department of Pathology, Inonu University School of Medicine, Malatya, Turkey; 2Department of Pharmacology, Inonu University School of Medicine, Malatya, Turkey; 3Department of Physiology, Inonu University School of Medicine, Malatya, Turkey; 4Department of Statistics, Firat University Faculty of Science, Elaziğ, TurkeyIntroduction and aim: Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats.Materials and methods: Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol–Mtx, and Mtx–Mol. Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using Roening grading and Bcl-2 antibody staining. Tissue oxidants, antioxidants, and serum transaminases were measured and statistically compared across all groups.Results: No hepatic fibrosis or steatosis was observed in any of the groups. In the Mtx group, grade 2 liver injury and score 2 Bcl-2 antibody staining were observed; however, in the Mol–Mtx group, these were lower (grade 1, score 1). There were no statistically significant differences in serum transaminase levels among groups. Malondialdehyde levels were higher in all rats that received Mtx, but no differences in myeloperoxidase levels were observed among the groups. Levels of tissue antioxidants, including superoxide dismutase, glutathione (GSH) peroxidase (GSH-Px), and reduced GSH, were significantly higher in the Mol-treated and Mol pre-treated groups. Catalase (CAT) levels were elevated in all Mol-treated groups, but only in that group were CAT levels statistically significantly higher than in the control group.Conclusion: Our results suggest that some oxidant levels could increase following Mtx administration in the liver, possibly contributing to liver damage, whereas Mol could mitigate the histopathological and biochemical effects of hepatotoxicity. However, molecular studies are required to understand the exact mechanisms of these alterations.Keywords: methotrexate, molsidomine, hepatotoxicity, hepatic fibrosis
