Tramadol Influences Cellular Metabolism and Autophagy in Germ and Sertoli Cells; Exercise Training as A Potential Ameliorative Strategy

Dysregulation of lipid and carbohydrate/fatty acid (FA) balance in Sertoli and germ cells alters the NADP+/ NADPH ratio, resulting in metabolic autophagy in testicles. Tramadol (TRA) adversely affects spermatogenesis development, and it is not reversed within short periods of time after withdrawal. Therefore, the present study aimed to examine the boosting effect of different exercise training protocols (ETPs) on TRA-induced detrimental effects after withdrawal. In this experimental study, 36 mature Wistar rats were separated into control and TRAsole (administered 40 mg/kg of TRA and euthanized 60 days after TRA administration), Con-TRA (stopped TRA administration after 60 days, and continued for additional 60 days after withdrawal), TRA+low-intensity (TRA+LICT), TRA+ moderate-intensity (TRA+MICT), and TRA+high-intensity continuous (TRA+HICT) ETPs-induced groups (n=6/ group, ETPs were initiated for 60 days after stopping TRA administration). Next, the intracytoplasmic carbohydrate and lipids/FAs content, testicular lactate and lactate dehydrogenase (LDH) levels, relative ratios of NADP+/NADPH, serum testosterone levels, and the Leydig cells steroidogenic activity, the mRNA levels of Beclin-1, p62, LC3-I, and Atg7 as well as the LC3-I/II+ germ and somatic cells mean distributions were analyzed. The LICT and MICT could ameliorate the TRA-induced carbohydrates/lipids, FAs imbalance, increase lactate, LDH and testosterone levels, re-balance the NADP+/NADPH ratio, and reregulate the autophagy and steroidogenic activities in the Leydig and Sertoli cells. Collectively, LICT and MICT can ameliorate the TRA-induced metabolic-oxidative autophagy by rebalancing energy survey in testicles and down-regulating autophagy reactions in Sertoli cells and rebalancing it in the Leydig cells.