High Intensity Interval Training (HIIT) Ameliorates the Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

Abstract

Abstract Introduction: Tramadol (TRA) is an opioid analgesic widely prescribed for moderate to severe pain; however, its chronic use is associated with kidney damage. Objectives: This study aimed to assess the impacts of high intensity interval training (HIIT) on the male rat's kidney following chronic TRA administration. Methods: In this experimental study, 30 male Wistar rats were assigned to the following groups: CON; animals received normal saline five days a week in the first month and three days a week second month, EXE; animals conducted (HIIT) according to exercise protocol five days a week for two months, TRA; animals received tramadol 50 mg/kg (i.p.) as described for the CON group. TRA-EXE; animals received tramadol and conducted exercise protocol, and EXE-SL; animals received normal saline and conducted exercise protocol. Then serum malondialdehyde (MDA), total antioxidant capacity (TAC), Glutathione peroxidase (GPx), superoxide dismutase (SOD), albumin (ALB), urea, creatinine (CR), and tissue level of TNFα, IL-6, IL-10 with pathological changes in kidney were measured. P < 0.05 was considered significant using Graph-pad Prism v.9. Results: Exercise in TRA-EXE group increased significantly IL-10, IL-6, MDA, urea, and CR levels compared with TRA group (but not compared to CON). As well, SOD, TAC, GPx, and ALB levels were decreased significantly in TRA-EXE compared with TRA group (but not compared to CON). Pathological findings showed increased inflammatory effect of HIIT even in EXE-TRA due to severe hyperemia seen in all exercise groups. Other findings were in line with the above results. Conclusion: The results showed that HIIT was able to reverse most of harmful effects of tramadol on kidney, including tramadol-induced apoptosis, oxidative stress, and kidney function indices. However, HIIT may lead to increased inflammation, unlike chronic use of tramadol which appeared to ameliorate inflammation. Finally, HIIT might be proposed as a therapeutic strategy for chronic users of tramadol.