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

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 investigat...

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Bibliographic Details
Main Authors: Viktorija Zitkute, Mindaugas Kvietkauskas, Vygante Maskoliunaite, Bettina Leber, Diana Ramasauskaite, Kestutis Strupas, Philipp Stiegler, Peter Schemmer
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/16/8373
Description
Summary: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, <i>Sprague-Dawley</i> rats were assigned to eight groups, including sham and IRI (<i>n</i> = 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 (<i>p</i> = 0.019) and glycine (<i>p</i> = 0.044) alone as well as their combination (<i>p</i> = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (<i>p</i> = 0.004), glycine (<i>p</i> < 0.001) or their combination (<i>p</i> < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (<i>p</i> = 0.027), glycine (<i>p</i> = 0.038) and combined treatment groups (<i>p</i> = 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.
ISSN:1661-6596
1422-0067