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. 2024 Nov 27;56(1):3.
doi: 10.1007/s10735-024-10286-2.

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

Wasim Akram  1 , Abul Kalam Najmi  1 , Syed Ehtaishamul Haque  2
Affiliations

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

Wasim Akram et al. J Mol Histol. .

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.

Keywords: Adjuvant therapy; Cyclophosphamide; Hepatic inflammation; Hepatotoxicity; Levocabastine; Oxidative stress.

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Conflict of interest statement

Declarations. Ethical approval: The experiment was approved by the Institutional Animal Ethics Committee (IAEC) with the protocol numbers 1930/1990. It complies with the ARRIVE guidelines and is carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments, or the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978). Competing interests: The authors declare no competing interests.

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