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Knowing the therapeutic effects of regular physical exercise on kidney toxicity induced by a single dose of doxorubicin (DOX) in animal models, the aim of this study is to verify the effectiveness of regular voluntary running on kidney histology after a prolonged DOX administration, mimicking a chemotherapy protocol. Thirty-four male Wistar rats were randomly divided into two clusters: DOX (n = 17) and SSS (sterile saline solution, n = 17), receiving a weekly intraperitoneal injection of DOX (2 mg/kg) or vehicle for 7 weeks, respectively. Two weeks after the last injection, five animals from each cluster (SSSG, n = 5; DOXG, n = 5) were euthanized, while the remaining ones were divided into sedentary (DOXsed, n = 6; SSSsed, n = 6) and active subgroups (DOXact, n = 6; SSSact, n = 6). Active animals were placed individually in cages with a running wheel for regular voluntary activity. After 2 months, the animals were euthanized and kidneys were histologically examined. Compared to SSSG, kidneys from DOXG revealed higher levels of damage, more collagen content and thickening of Bowman’s capsule (p < .05). The levels of damage and thickness of Bowman’s capsule increased in DOXsed as compared to DOXG (p < .05). Compared to DOXsed, the DOXact presented an overall improvement in kidney structure (p < .05), with a decrease in collagen content and of the thickness of Bowman’s capsule. The results allow concluding that regular voluntary running attenuate the long-term harmful effects on kidney structure induced by a prolonged DOX treatment. These results, supporting the potential benefit of physical activity in patients under DOX treatment, need to be tested in humans. [ABSTRACT FROM AUTHOR]