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Diabetic kidney disease (DKD) has emerged as a significant global health concern, standing as the leading cause of terminal chronic kidney disease (CKD). The use of nephrotoxic drugs, such as polymyxin B (PmB), escalates risks for individuals with DKD, precipitating acute kidney injury (AKI) and further exacerbating the disease's trajectory. Physical exercise (PE) is a non-pharmacological intervention capable of alleviating DKD-associated complications, providing a promising perspective for reducing its morbidity. Objective: To assess the impact of PE on renal function, hemodynamics, oxidative profile and histology in rats with DKD that received PmB.
It was employed adult male Wistar rats, weighing 280-300 g, categorized as follows: Citrate (CT): animals receiving streptozotocin vehicle (citrate; i.v., caudal, single dose, 1st day of experimental protocol); Citrate+PE: citrate animals subjected to daily swimming training (1 hour, with 5% of body weight attached to the tail, 4 weeks); Diabetes Mellitus (DM): animals that received streptozotocin (STZ, 60 mg/kg; i.v.; single dose, 1st day of experimental protocol, followed up to the 28th day); DM+PE: DM animals subjected to swimming traning; DM+PmB: DM animals receiving PmB (4 mg/kg/day, i.p., once a day, 5 days); DM+PE+PmB: DM animals receiving PmB and subjected to PE. Renal function (serum creatinine-CrS; inulin clearance-Clin and microalbuminuria), renal hemodynamics (renal blood flow-RBF and renal vascular resistance-RVR), oxidative profile (urinary peroxides, lipid peroxidation, urinary nitrate, and thiols) and renal histology were evaluated.
The DM+PmB group exhibited a reduction on Clin, RBF and renal thiol levels, while CrS, microalbuminuria, RVR, the excretion of oxidative metabolites and tubulointerstitial injury score significantly increased. PE emerged as a counterbalance, attenuating the deterioration of renal function in the DM groups preventing hemodynamic alterations, in addition to reducing oxidative stress and tubulointerstitial injury score.
Findings revealed that exercised animals did not manifest AKI when exposed to additional insult by PmB. PE confirmed its renoprotective effect, providing a relevant positive effect on DKD morbidity in rats exposed to PmB-induced nephrotoxicity. These results not only offer an innovative insight into the interplay between PE and nephrotoxicity in DKD and the renal disease morbidity, but also pave the way for promising interventions in the treatment and management of Diabetic Kidney Disease.