Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia

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.

Glycine protects the male reproductive system against lead toxicity via alleviating oxidative stress, preventing sperm mitochondrial impairment, improving kinematics of sperm, and blunting the downregulation of enzymes involved in the steroidogenesis

“…Several studies mentioned the protective properties of glycine in other organs such as the heart, kidney, uterus, liver, and skeletal muscle. 47,[104][105][106][107] In line with previous investigations on the antioxidative stress properties of glycine, we found that this amino acid significantly decreased oxidative stress biomarkers in Pb-treated animals. These studies indicate that the effects of glycine on oxidative stress parameters play a fundamental role in its protective properties.…”

“…Moreover, the antioxidants levels were significantly higher in glycine‐treated groups (Figure 4). Several studies mentioned the protective properties of glycine in other organs such as the heart, kidney, uterus, liver, and skeletal muscle 47,104–107 . In line with previous investigations on the antioxidative stress properties of glycine, we found that this amino acid significantly decreased oxidative stress biomarkers in Pb‐treated animals.…”

Relaxin and Erythropoietin Significantly Reduce Uterine Tissue Damage during Experimental Ischemia–Reperfusion Injury

“…In essence, the same results were achieved by Atalay et al by continuously administering remifentanil during ischemia-reperfusion [20]. Recently, the use of melatonin and glycine was shown to significantly reduce tissue MPO expression and increased SOD activity [21].…”

Involving Animal Models in Uterine Transplantation

“…Warm ischemia can cause permanent damage if it lasts more than 4 h. Within 3 h, there were no histological or functional injuries, and these results that are transposable to the humans. In rats, the injection of Melatonin and Glycine ( 42 ), Remifentanil ( 41 ), or cannabinoid agonist JWH-133 ( 43 ) reduced warm ischemia-reperfusion injuries.…”