The protective effects of trimetazidine on testicular ischemia and reperfusion injury in rats

This study was designed to investigate the protective effect of trimetazidine [TMZ; 1-(2, 3, 4-trimethhoxibenzyl)-piperazine dihydrochloride], as an antioxidant agent, on torsion-detorsion-induced biochemical and histopathological changes in experimental testicular ischemia/reperfusion injury in rats. Twenty-seven male Wistar rats weighing 180-220 g were divided into five groups: control (C, n = 4), sham-operated (S, n = 4), ischemia (I, n = 6), ischemia-reperfusion (I/R, n = 6) and ischemia-reperfusion + trimetazidine (I/R + TMZ; n = 7). Control rats were used for basal normal values. In group I, 2 h torsion of the left testis was performed. In I/R and I/R + TMZ groups, following 2 h of torsion, 4 h detorsion of the testis was performed. In ischemia and I/R groups, physiologic saline was administered orally for 7 days, and the rats in I/R + TMZ group were pretreated orally with 5 mg/kg day TMZ for 7 days before inducing ischemia. At the end of each experiment, ipsilateral orchiectomies were performed for the tissue levels of malondialdehyde (MDA), glutathione peroxidase (GPx) enzyme activities and histopathological examinations in all groups. MDA levels were significantly reduced and GPx enzyme activities were significantly increased in testes in I/R+TMZ pretreated group compared to group I and I/R. The mean seminiferous tubular diameter (MSTD) and Johnsen's score were significantly better in I/R+TMZ group than groups I and I/R. Pretreatment with TMZ decreased germ cell apoptosis and caspase-3 expression in the ischemic testis. The present results show that TMZ has a protective activity in the testicular injury caused by I/R, and provide the first evidence of the role of TMZ for the prevention of I/R-induced testicular injury.