Abstract
Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.
Highlights
Successful uterus transplantation (UTx) has been shown to be the best treatment option for patients with absolute uterus factor infertility (AUFI) [1]
Uterus Ischemia/reperfusion injury (IRI) led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001)
Melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI
Summary
Successful uterus transplantation (UTx) has been shown to be the best treatment option for patients with absolute uterus factor infertility (AUFI) [1]. In 2014, Brännström et al reported the first human live birth following UTx, arousing interest in research on UTx as AUFI treatment and resulting in at least 20 clinical trials and even more animal experiments currently taking place across the world [5]. The need for UTx is growing in addition to the increasing number of successful clinical trials worldwide. About 100 human UTx have been performed with around 20 reported successful live births [2]. UTx is still at the stage of animal experiments and clinical trials, its necessity is undeniable, and it is only a matter of time before this procedure becomes routine worldwide
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