Levocabastine ameliorates cyclophosphamide-induced hepatotoxicity in Swiss albino mice: modulation of Nrf2, NF-κB p65, cleaved caspase-3 and TGF-β signaling molecules

Abstract

Background

Cyclophosphamide (CP)-induced hepatotoxicity is a significant problem in clinical settings. This study aimed to evaluate the protective effect of levocabastine (LEV) on CP-induced hepatotoxicity in Swiss albino mice.

Methods and results

Mice were given CP (toxic drug) 200 mg/kg, i.p., once on the 7th day, and LEV 50 and 100 µg/kg, i.p., and fenofibrate (FF) 80 mg/kg, p.o., daily for 14 days. On the 15th day, blood and liver samples were collected to assess biological parameters. CP 200 mg/kg caused hepatotoxicity due to oxidative stress, inflammation, apoptosis, and fibrosis as manifested by a reduction in catalase, reduced glutathione (GSH), superoxide dismutase (SOD), and an increase in thiobarbituric acid reactive substance (TBARS), nitrite, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-β1), interleukin-1β (IL-1β), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels. Cleaved caspase-3 and nuclear factor kappa-B (NF-κB) expression was also increased and nuclear factor erythroid 2-related factor (Nrf2) expression was decreased as confirmed by Immunohistochemical analysis. It also caused histopathological abnormalities and fibrosis as manifested by Hematoxylin-Eosin (H&E) and Masson’s trichrome (MT) staining. These alterations were returned to almost normal when treated with LEV 100 µg/kg and FF 80 mg/kg. Thus, LEV protected CP-induced hepatotoxicity by reversing inflammation, apoptosis, fibrosis, oxidative stress, hepatic injury, and histopathological damages.

Conclusion

LEV can be helpful as an adjuvant in cancer patients who are on CP treatment, to minimize toxicity. However, its role in in-vivo cancer model is further needed to be confirmed.