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

• Tipo de documento: Artigo Científico
• Fonte: ANTIOXIDANTS; v. 12, n. 5, p. 21-pg., 2023-04-26.

Resumo

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)

• Processo FAPESP: 18/07383-6 - Sinalização pela quinase de adesão focal em miócitos cardíacos: novas interações proteicas e funções celulares
• Beneficiário: Aline Mara dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/11824-8 - Microscopias de super resolução aplicadas ao estudo do papel da tirosina quinase 2 (PTK2) e da família de miosinas V a reposta ao dano no DNA em cardiomiócitos submetidos ao estresse genotóxico
• Beneficiário: Andre Alexandre de Thomaz
• Modalidade de apoio: Auxílio à Pesquisa - Regular