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Uroprotective Potential of Campesterol in Cyclophosphamide Induced Interstitial Cystitis; Molecular Docking Studies.

Authors :
Javed J
Anjum I
Najm S
Ali N
Nasir Hayat Malik M
Jahan S
Dawoud TM
Nafidi HA
Bourhia M
Source :
Chemistry & biodiversity [Chem Biodivers] 2023 Dec; Vol. 20 (12), pp. e202301534. Date of Electronic Publication: 2023 Nov 28.
Publication Year :
2023

Abstract

Cyclophosphamide (CYP) is commonly used to treat cancer of the ovaries, breast, lymph, and blood system and produces interstitial cystitis (IC) via its urotoxic metabolite: i. e., acrolein. The present study was aimed to investigate the uroprotective effect of campesterol (a steroidal phytochemical) in cyclophosphamide induced IC. IC was induced by CYP (150 mg/kg, i. p.) in rats. The Enzyme linked immunosorbent assays for oxidative stress markers and Polymerase Chain Reaction (PCR) for inflammatory cytokines were carried out. The Tissue Organ Bath Technique was used for the evaluation of the spasmolytic effect of campesterol. Different pharmacological antagonists have been used to explore the mechanism of action of campesterol. Treatment with campesterol (70 mg/kg) reduced nociception (55 %), edema (67 %), hemorrhage (67 %), and protein leakage significantly (94 %). The antioxidant activity of campesterol was exhibited by a fall in MDA, NO, and an elevation in SOD, CAT, and GPX levels. Campesterol presented anti-inflammatory potential by decreasing IL-1, TNF-α, and TGF-β expression levels. Histologically, it preserved urothelium from the deleterious effect of CYP. Campesterol showed a spasmolytic effect by reducing bladder overactivity that was dependent on muscarinic receptors, voltage-gated calcium and K <subscript>ATP</subscript> channels, and cyclo-oxygenase pathways. In silico studies confirmed the biochemical findings. The findings suggest that campesterol could be valorized as a possible therapeutic agent against cyclophosphamide-induced interstitial cystitis.<br /> (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Details

Language :
English
ISSN :
1612-1880
Volume :
20
Issue :
12
Database :
MEDLINE
Journal :
Chemistry & biodiversity
Publication Type :
Academic Journal
Accession number :
37984454
Full Text :
https://doi.org/10.1002/cbdv.202301534