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Drug Res (Stuttg)
DOI: 10.1055/a-2552-2486
Original Article

Levocabastine ameliorates cyclophosphamide-induced nephrotoxicity in Swiss albino mice via NF-κB/cleaved caspase-3/TGF-β signaling pathways

Wasim Akram
1   Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
,
Abul Kalam Najmi
1   Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
,
M.Mumtaz Alam
2   Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
,
Syed Ehtaishamul Haque
1   Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
› InstitutsangabenGefördert durch: ICMR-SRF 45/26/2022-PHA/BMS
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Abstract

Cyclophosphamide (CP) is a potent anticancer drug, but nephrotoxicity is one of the vital organ toxicities that it causes as a side effect. We tried to evaluate the nephroprotective effect of levocabastine (LEV) in CP-induced nephrotoxicity in Swiss albino mice. Mice were given CP 200 mg/kg, i.p., once on the 7th day. LEV (0.05 and 0.1 mg/kg, i.p.) and fenofibrate (FF) (80 mg/kg, p.o.) were given daily for 14 days. On the 15th day, animals were sacrificed and kidneys were removed for examination. The docking study showed significant binding of LEV and FF against TGF-β1, which is a prime target molecule involved in nephrotoxicity. CP 200 group showed nephrotoxicity in terms of oxidative stress, apoptosis, inflammation, and fibrosis as manifested by decreased levels of SOD, catalase, GSH, blood urea nitrogen/creatinine (BUN/Cr) ratio, and increased TBARS, nitrite, TNF-α, IL-6, TGF-β1, IL-1β, urea, uric acid, creatinine, and BUN. A decrease in body weight (BW) and an increase in kidney weight (KW) with an increased KW/BW ratio was also observed. Cleaved caspase-3 and NF-κB expression was also increased. Histopathological aberrations, like renal corpuscle damage, Bowman’s space widening, glomerulus, mesangium cell disintegration, atrophic podocytes, vacuolation, and fibrotic changes were also seen. LEV 0.1 and FF 80 significantly reversed these changes toward normal and showed nephroprotective potential. Thus, seeing the protective effect of LEV on CP-intoxicated mice, we conclude that LEV may be used as an adjuvant with CP in cancer, however, it needs more studies with the direct cancer model to confirm the claim.

Keywords

renal toxicity - levocabastine - cyclophosphamide - oxidative stress - renal inflammation - fenofibrate


Publikationsverlauf

Eingereicht: 26. September 2024

Angenommen: 24. Februar 2025

Artikel online veröffentlicht:
14. April 2025

© 2025. Thieme. All rights reserved.

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