The Isopropyl Gallate Counteracts Cyclophosphamide-Induced Hemorrhagic Cystitis in Mice

• Published in: Biology (Basel, Switzerland) Vol. 11; no. 5; p. 728
• Main Authors: Almeida de Oliveira, Lucas Solyano, de Moura Bandeira, Sara Raquel, Gomes Gonçalves, Rodrigo Lopes, Pereira de Sousa Neto, Benedito, Carvalho de Rezende, Diana, Dos Reis-Filho, Antonio Carlos, Sousa, Ian Jhemes Oliveira, Pinheiro-Neto, Flaviano Ribeiro, Timah Acha, Boris, do Nascimento Caldas Trindade, Gabriela, do Nascimento, Lázaro Gomes, de Sousa, Damião Pergentino, de Castro Almeida, Fernanda Regina, Lucarini, Massimo, Durazzo, Alessandra, Arcanjo, Daniel Dias Rufino, de Assis Oliveira, Francisco
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-05-2022; MDPI
• Subjects: Acids; Acrolein; Alcohol; Animals; Anti-inflammatory agents; antineoplastic chemotherapy; Antioxidants; Bladder; C-reactive protein; Chemotherapy; Chromatography; Cyclophosphamide; Cystitis; Cytotoxicity; Edema; Gallic acid; Hemoglobin; Hemorrhage; Hemorrhagic cystitis; Ifosfamide; IL-1β; Inflammation; isopropyl gallate; Oral administration; Oxidative stress; Permeability; Potassium; Side effects; Sodium; Tumor necrosis factor-α; Tumors; Urinary bladder; isopropyl gallate; ifosfamide; hemorrhagic cystitis; antineoplastic chemotherapy
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology11050728

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.