Efeito Protetor da Corrida Voluntária Regular na Toxicidade Hepática Induzida pela Administração Prolongada de Doxorrubicina em Ratos Wistar

Abstract

In last decades, cancer becomes more progressive, acquiring today, in the western countries, an epidemic character. Doxorubicin (DOX), an anthracycline used in several cancer treatments, is associated with the appearance of several undesirable side effects resulting from its toxicity in the most diverse organs and tissues in cancer survivors. The metabolism of some drugs, in particular DOX, in short and long-term become harmful to liver tissue, resulting in its dysfunction. However, regular physical activity (RAF) could be used as a therapeutic resource to reduce these harmful effects. Several studies have demonstrated the benefits of regular exercise (RE) in the decrease of DOXinduced liver toxicity in healthy rats, particularly in the parameters discussed above. The aim of this study was to characterize the hepatic toxicity resulting from the prolonged administration of DOX mimicking a chemotherapy protocol, and to verify if a regular voluntary exercise performed posteriori can reverse it in Wistar rats. Forty male Wistar rats were randomly divided into 2 clusters: 1) treated with an intraperitoneal (ip) injection of 3 mg / kg DOX for 7 weeks (n = 17) and 2) treated with an ip injection / week of sterile saline solution (SSS), for 7 weeks (n = 17). After two weeks of the last injection, 5 animals from each cluster were sacrificed (SSSG, n = 5, DOXG, n = 5), the remaining were divided into 2 subgroups: 1) sedentary (DOXsedG, n = 6; = 6), housed in cages without wheel for voluntary running, and 2) active (DOXexeG, n = 6; SSSexeG, n = 6) housed in cages with free wheel acess for voluntary running. At the end of 8 weeks, animals were sacrificed and hepatic samples were taken to histologically assess, to measure the degree of hepatic damage as well as their collagen content. The results revealed that the DOXG animals showed a general marked steatosis and a higher inflammation compared to the SSSG group. At long-term, in DOXsedG group there was a pronounced sinusoidal dilatation, numerous necrotic zones and an abundant infiltration of blood cells, with the SSSsedG group evidencing a normal structure.In DOXexeG animals, histological changes were significantly lower than the DOXsedG group. The results allow us to conclude that a prolonged DOX administration, mimicking a chemotactic treatment, has short (DOXG vs SSSG) and long-term (DOXsedG vs SSSsedG) toxic effects, and regular voluntary running, performed after administration of DOX, attenuates long-term toxic effects of the liver.