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
