Influência da suplementação com L-arginina na remodelação cardíaca de ratos submetidos ao 5-fluorouracil

Abstract

Cardiac remodeling (REM) is a condition that affects cardiomyocytes, blood vessels and the extracellular matrix (ECM), and may be the result of numerous factors such as cardiomyopathies and antioneoplastic drugs. 5-fluorouracil (5-FU) is one of these drugs, used to treat cancers of the breast, head, neck and esophagus, it is an antimetabolite chemotherapy that is related to cardiotoxicity by promoting ischemia. L-arginine (ARG), a semi-essential amino acid synthesized in the small intestine and kidneys, has been used as a supplement and cooperative in the presence of diseases that affect the cardiovascular system and could be a cardioprotective therapeutic resource applied in this condition. Therefore, the objective of this work was to evaluate the effect of low doses of L-arginine supplement on REM in Wistar rats submitted to chemotherapy with 5-FU. 48 male rats with 40 days of age, average body weight of 140 ± 10g were used, divided into 4 groups, n = 12 each group: control (CT): treated with saline, group 5-FU (1 dose of 200 mg ), ARG group: preventively treated with ARG (100mg) in filtered water and 5-fluorouracil + L-arginine (5-FU + ARG). After euthanasia, 72 hours after the introduction of chemotherapy, the heart was weighed, dissected and processed for histological analysis and gene expression. The rats treated with 5-FU, ARG and ARG + FU showed a reduction in body weight and none of the groups presented hypertrophy. There was a reduction in fractability and improvement in cell organization in the ARG + 5-FU group and the group treated only with ARG showed fibrosis. The gene expression of collagens (Col) 1a1, 1a2 and 3, of the vasodilation marker (Nos 3) and of the inducible hypoxia factor (Hif1-α) showed a reduction in rats submitted to chemotherapy. The association 5- FU + ARG did not alter this decrease. We concluded that only one session of 5-fluorouracil promoted altered cardiac gene expression and that its association with L-arginine did not reverse the decrease in collagen, nitric oxide and the inducible hypoxia factor.