The Isopropyl Gallate Counteracts Cyclophosphamide-Induced Hemorrhagic Cystitis in Mice.

Abstract

Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory cytokines, which culminate in injury of the bladder tissue. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. The induction of the hemorrhagic cystitis model was carried out using a single dose of IFOS (400 mg/kg, i.p.) four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Mesna (positive control; 80 mg/kg, i.p.) was administered four hours before and eight hours after induction of cystitis. In the present study, IPG 25 mg/kg significantly decreased edema and hemorrhage, with a reduction of the bladder wet weight (36.86%), hemoglobin content (54.55%), and peritoneal vascular permeability (42.94%) in urinary bladders of mice. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF-α (88.77%), IL-1β (62.87%), and C-reactive protein (56.41%) levels. Our findings demonstrate that IPG has a substantial protective role against IFOS-induced hemorrhagic cystitis in mice by enhancing antioxidant activity and proinflammatory mechanisms. Thus, IPG represents a promising co-adjuvant agent in oxazaphosphorine-based chemotherapy treatments.

• Authors: Lucas Solyano Almeida de Oliveira, Sara Raquel de Moura Bandeira, Rodrigo Lopes Gomes Gonçalves, Benedito Pereira de Sousa Neto, Diana Carvalho de Rezende, Antonio Carlos Dos Reis-Filho, Ian Jhemes Oliveira Sousa, Flaviano Ribeiro Pinheiro-Neto, Boris Timah Acha, Gabriela do Nascimento Caldas Trindade, Lázaro Gomes do Nascimento, Damião Pergentino de Sousa, Fernanda Regina de Castro Almeida, Massimo Lucarini, Alessandra Durazzo, Daniel Dias Rufino Arcanjo, Francisco de Assis Oliveira
• Journal: Biology (Biology (Basel)) Vol. 11 Issue 5 (May 09 2022) ISSN: 2079-7737 [Print] Switzerland
• PMID: 35625456 (Publication Type: Journal Article)