The effect of antioxidants on angiogenesis in uterine transplantation

Abstract

The aim of this study was to investigate the effect of antioxidants on angiogenesis in uterine transplantation. We used 24 female rats equally divided into four groups: Group 1 had the uterus stored in HTK (Histidine-Tryptophan-Ketoglutarate) solution at 4 °C cold storage for 4 h. Group 2 had the uterine tissue stored in HTK solution combined with acetyl L-carnitine (10M) for 4 h at +4 °C. The same procedures with Group 1 and 2 were repeated for 24 h for Groups 3 and 4, respectively. Histological investigation and immunohistochemical analysis were performed. Histological findings showed that storing donor uterus in HTK solution at +4° C for 24 h results in histological alteration in uterus. We also found that immunoreactivity of VEGFR-2 in all layers of rat uterus in Group 2 was lower than that in Group 1, and the expression of the uterus in Group 4 was lower than that in Group 3. We concluded that antioxidant acetyl L-carnitine, which was added to the organ preservation solution HTK, had prevented the formation of free radicals, and thus protected the uterus that was stored in short and long cold storage periods. Impact statement What is already known on this subject? Ischemia-reperfusion is a complex pathophysiological process involve in hypoxia and/or reoxygenation, ionic imbalance-induced oedema and acidosis, oxidative stress, mitochondrial uncoupling, coagulation and endothelium activation. The composition of preservation solutions must be adapted to the severity of ischaemia-reperfusion injuries to reduce cellular damage and inflammation and preserve graft functionality and integrity, thus improving short-term and long-term graft outcome. Clinicians use three types of composition of solution for static cold preservation: intracellular, intermediate and extracellular. HTK will be used frequently, especially with the consideration of lower price and more easy handling aspects. L-carnitine acts as an antioxidant, protects against free radicals and prevents mitochondrial damage. VEGFR-2 plays an important role in angiogenesis, chemotaxis, proliferation and migration of endothelial cells. What this study adds? In this study, we investigate the effect of antioxidants on angiogenesis in uterus transplantation. Our results showed that antioxidant acetyl L-carnitine that added to the organ preservation solution HTK, has prevented the formation of free radicals, thus protect the uterus that was stored in short and long cold storage periods. What the implications are for future studies? Therefore, we will contribute to the literature with the results of this study.

Involving Animal Models in Uterine Transplantation

“…Custodiol-N ( 45 ) was better than Custodiol for uterine preservation in rats. Adding acetyl L-carnitine to a Histidine-Tryptophan-Ketoglutarate solution prevented the formation of free radicals ( 44 ). Perfadex® ( 10 ) containing colloid and dextran 40 was better than saline solution for UTx in sheep.…”

The Key Role of Warm and Cold Ischemia in Uterus Transplantation: A Review

“…HTK, an extracellular solution, is characterized by low concentrations of sodium and potassium, whereas UW and Euro-Collins solutions, which have also been used for UTx in humans, have higher potassium concentrations and potentially deleterious effects on the graft [65]. In addition, a study by Ugurlu et al [38] shows that the protective effect of a storage fluid can be improved further by adding pharmacological agents, which may make it possible to increase the storage time of organs. However, other comparative studies are required to determine which storage fluid is the most appropriate for UTx.…”

“…One recent study focused on the possibility of improving uterine CI tolerance by adding an antioxidant, acetyl L-carnitine, to the storage fluid [38]. Rat uteri ( n = 24) were stored for 4 or 24 h in histidine-tryptophan-ketoglutarate (HTK) solution, with or without acetyl L-carnitine (4 groups).…”

Pharmacological Benefits and Risk of Using Hormones in Organ Perfusion and Preservation Solutions in the Aspect of Minimizing Hepatic Ischemia-Reperfusion Injury during Storage

“…It protects against oxidative stress, mitochondrial damage, and alterations in vascular resistance [32]. HTK (Bretschneider's solution, Custodiol) is an intracellular fluid, crystalloid, used to store the heart, liver, kidneys, and pancreas [33]. Its task is to counteract the retention of sodium and calcium ions in the intracellular space and buffer the extracellular space by means of the histidine/histidine HCl system during organ ischemia [34].…”