Effects of melatonin and metformin co-administration on testicular ischemia/reperfusion injury in rats

SummaryIntroductionTorsion of the spermatic cord is a common urologic emergency among infants and adolescents. It requires early diagnosis and surgical intervention to prevent subfertility and infertility.ObjectiveThe aim of this study was to investigate the effects of melatonin (MEL) and metformin (MET) co-administration on experimental testicular ischemia/reperfusion (I/R) injury in rats.Material and methodsFifty male Wistar rats were randomly divided into five experimental groups (n = 10), as follows. Group 1 was sham operated. In group 2, 1-hour ischemia was induced by the left testicular artery and vein clipping followed by 7 days of reperfusion. In groups 3 and 4, MEL (3 mg/kg) or MET (100 mg/kg) was administered orally for 7 days via oral gavage after ischemia, and in group 5 both agents were co-administered. At the end of trial, the left testis was removed for histological analysis and oxidative stress measurement. Histological findings in seminiferous tubule were evaluated according to Johnsen's scoring system.ResultsI/R reduced superoxide dismutase (SOD) activities and testicular Johnsen's scores accompanied by an elevation in malondialdehyde (MDA) and myeloperoxidase (MPO) levels (p < 0.05). MEL and MET, and their combination restored SOD activity, tissue scores, MDA and MPO levels (p < 0.05). There was no significant difference among individual or combined treatment of these parameters (p > 0.05).DiscussionIn the present experiment, using a rat model it has been demonstrated that testicular I/R caused a significant increase in testicular injuries. This was in accordance with previous studies that have demonstrated the effect of I/R in testicular tissue. Treatment of MEL and MET had a benefit effect, but, there was no significant difference among individual or combined treatment.ConclusionsThe results of the present study suggest that MEL and MET may be useful for protecting the testes from the I/R injury. However, the combined use of these agents does not further increase the protection from this damage.Table. Histological scores in the experimental groups.GroupHistological scoreSham9.95 ± 0.16Ischemia/reperfusion2.99 ± 0.12*Melatonin8.50 ± 0.52Metformin8.30 ± 0.52Melatonin + metformin8.67 ± 0.53* p < 0.05 compared with the other groups.