Uro-protective role of chrysin against cyclophosphamide-induced hemorrhagic cystitis in rats involving the turning-off NF-κB/P38-MAPK, NO/PARP-1 and STAT-3 signaling cascades

Abstract

Chemico-Biological Interactions Available online 30 May 2023, 110585 In Press, Journal Pre-proofWhat’s this? Research paper Uro-protective role of chrysin against cyclophosphamide-induced hemorrhagic cystitis in rats involving the turning-off NF-κB/P38-MAPK, NO/PARP-1 and STAT-3 signaling cascades Author links open overlay panelDalia O. Saleh a, Nesma M.E. Abo El Nasr a, Ahmed M. Fayez b, Kawkab A. Ahmed c, Reem A. Mohamed d a Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt b Pharmacology and Toxicology Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt c Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt d Department of Pharmacology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt Received 2 March 2023, Revised 6 May 2023, Accepted 29 May 2023, Available online 30 May 2023.

Show less Outline Share Cite https://doi.org/ Background Chemotherapeutic agents are used to treat a wide range of cancer types, but they cause serious side effects which must be managed after treatment. Cyclophosphamide (CYP) is one of chemotherapeutic drugs that causes hemorrhagic cystitis (HC) induced by acrolein.

Objective The current investigation intended to uncover the role of chrysin (CHR) in CYP-induced HC in rats and explore the signaling pathway beyond this effect.

Analysis process: A single dose of CYP (200 mg/kg/IP) was injected, meanwhile CHR (25, 50 and 100 mg/kg, P.O) was administered respectively for 7 days prior to CYP administration and resume for 7 days afterwards. Urinary bladder tissue was then isolated from all rats to assess oxidative stress and inflammatory biomarkers. Moreover, histopathological examinations were performed.

Results Treatment with CHR showed a marked alleviation in oxidative stress biomarkers induced by CYP. Furthermore, CHR treatment presented a dose-dependent boost in the anti-inflammatory; IL-10 levels and a drop in the pro-inflammatory biomarkers; IL-1β, IL-6, and TNF–α. Additionally, stabilization of the PARP-1 protein expression was also detected thus preventing DNA damage. Similarly, CHR restored the urinary bladder cGMP levels. Notably, CHR treatment was accompanied with inhibition in NF-κB/p38-MAPK, NO/PARP-1 and STAT-3 signaling pathways inflammatory cascades. All these findings conformed with the histopathological examinations as well as iNOS immunostaining in the urinary bladder tissue.

Conclusion Co-administration of CHR and CYP attained uro-protective therapeutic potential to guard against HC as well as spot the tangled mechanism of CHR in attenuating the HC induced by CYP.