A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs

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da Silva, Mariana Conceicao ; Fabiano, Lilian Catarim ; da Costa Salomao, Karile Cristina ; de Freitas, Pedro Luiz Zonta ; Neves, Camila Quaglio ; Borges, Stephanie Carvalho ; Carvalho, Maria das Gracas de Souza ; Breithaupt-Faloppa, Ana Cristina ; de Thomaz, Andre Alexandre ; dos Santos, Aline Mara ; Buttow, Nilza Cristina

• Document type: Journal article
• Source: ANTIOXIDANTS; v. 12, n. 5, p. 21-pg., 2023-04-26.

Abstract

5-Fluorouracil (5-FU) is a chemotherapy drug widely used to treat a range of cancer types, despite the recurrence of adverse reactions. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. On the 15th day, blood, liver, kidney, and lung samples were collected for histological, oxidative stress, and inflammatory evaluations. We observed a reduction in the antioxidant markers and an increase in lipid hydroperoxides (LOOH) in the liver of treated animals. We also detected elevated levels of inflammatory markers, histological lesions, apoptotic cells, and aspartate aminotransferase. Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. 5-FU reduces endogenous antioxidant defenses and increases LOOH levels in the lungs, suggesting oxidative stress. Inflammation and histopathological alterations were also detected. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. These results will be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in such organs. (AU)

• FAPESP's process: 18/07383-6 - Focal adhesion kinase signaling in cardiac myocytes: new protein interactions and cell functions
• Grantee: Aline Mara dos Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/11824-8 - Super resoulution microscopies applied to the study of tirosin kinase 2 (PTK2) and miosin V family roles in the DNA damage response in cardiomiocites under genotoxic stress
• Grantee: Andre Alexandre de Thomaz
• Support Opportunities: Regular Research Grants