Benefits of regular physical activity on Doxorubicin-induced Kidney Toxicity

Abstract

Doxorubicin (DOX), an anthracycline used in cancer treatments, has a lot of side-effects, such us the capacity for induce high levels of toxicity on tissues and organs of patients and cancer survivors. Renal demage, increasing collagen deposition and the thickness of bowman's capsule (TBC) are some side-effects which occurs after a chemotactic treatment, and most of them are connected with renal dysfunction and failure. However, it is well documented that regular physical activity is important to reduce the side-effects, and could be used as a therapy improving renal structure and function on rats and humans. Several studies have verified the benefit effects of regular physical activity practice on the reduction of kidney toxicity in healthy rats, decreasing their levels of damage, collagen content and also decrease the thickness of bowman's capsule. The aim of this study was to understand the mechanisms underlying DOX-induce kidney toxicity and verify if physical exercise practice could be used to improve and revert these side-effects caused by a prolonged DOX administration on healthy rats. Thirty-four male Wistar rats were randomly divided into 2 clusters: 1) one treated with doxorubicin (DOX, n=17), which received weekly an intraperitoneal (i.p.) injection of 2 mg/kg of DOX for 7 weeks, and 2) the other treated with sterile saline solution (SSS, n=17) that received i.p. injections of vehicle during 7 weeks. Two weeks after the last injection, five animals from each group (SSSG, n=5; DOXG, n=5) were euthanized while the remaining rats were subsequently divided into sedentary (DOXsedG, n=6; SSSsedG, n=6) and active subgroups (DOXactG, n=6; SSSactG, n=6). Both groups placed individually in cages during 2 months, however the cages of active animals were equipped with a run wheel for voluntary running. At the end of the protocol, animals were euthanized and kidneys were histologically examined. The results revealed higher levels of renal damage, collagen deposition and an increase of TBC at short-term, on DOXG animals comparatively with SSSG group (p<.05) While, at long-term it was observed higher levels of damage and an increase of TBC (p<.05)., however the collagen content remain similar between DOXG and DOXsedG groups. On active group, compared with DOXsedG, a decreased of renal damage, collagen content andthe TBC (p<.05) was observed. These results allow concluding that regular voluntary running, applied after a prolonged DOX administration, is effective to attenuate the harmful effects of this drug in kidneys.