High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats.

ABSTRACT

INTRODUCTION: Tramadol (TRA) is an opioid analgesic widely prescribed for moderate-to-severe pain; however, its abuse and chronic use have been associated with kidney damage. Considering the protective role of exercise training in reducing organ damage, this study aimed to assess the influence of high-intensity interval training (HIIT) on a male rat's kidney following chronic TRA administration. METHODS: In this experimental study, 30 male Wistar rats were assigned to the following groups control (CON; animals received normal saline five days a week in the first month and three days a week in the second month), exercise (EXE; animals conducted HIIT training according to exercise protocol five days a week for two months), TRA (animals received TRA 50 mg/kg (i.p.) as described for the CON group), EXE-TRA (animals received TRA and conducted exercise protocol), and EXE-SL (animals received normal saline and conducted exercise protocol). Then, serum IL-6 and IL-10 levels, tissue malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and levels of albumin, urea, and creatinine (CR), along with pathological changes in the kidney, were measured. A p-value of <0.05 was considered significant using GraphPad Prism v.9 (GraphPad Software, La Jolla, California, USA). RESULTS: The inflammatory cytokines IL-6 and IL-10 were significantly increased in the EXE and EXE-TRA groups compared to the TRA group. Chronic administration of TRA in the TRA group decreased antioxidant indicators TAC, GPx, and SOD in kidney tissue while increasing oxidative stress MDA compared to the CON group (p<0.05). In contrast, the EXE-TRA group showed higher levels of TAC, GPx, and SOD, while MDA decreased compared to the TRA group. Additionally, serum levels of urea and CR were increased in the TRA group compared to the CON group, whereas these levels were decreased in the EXE-TRA group compared to the TRA group. The inflammatory effect of HIIT training, due to severe hyperemia and mild inflammatory cell infiltration, was seen in all EXE groups. Pathological findings confirmed TRA-induced kidney damage through moderate hyaline cast presence and severe apoptosis in the TRA group. Other findings were in line with the above results. CONCLUSION: These findings confirm the nephrotoxicity of chronic use of TRA through biochemical and oxidative markers and pathological outcomes. In addition, the result suggests that HIIT has the potential to mitigate the detrimental effects of TRA through reversing biochemical and oxidative markers, including TRA-induced apoptosis. Consequently, considering its restorative properties, HIIT could be explored as a prospective nephroprotective approach for long-term TRA treatment.