The effect of antioxidants on angiogenesis in uterine transplantation.

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 (10-8 M) 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.

Examining the protective effects of acetyl l-carnitine on cisplatin-induced uterine tube toxicity.

The aim of this study was to investigate the effects of cisplatin and the protective role of acetyl l-carnitine against uterine tube toxicity. Twenty-four female Wistar albino rats were divided into four groups: control group was injected with saline (control); group 2 was injected with acetyl l-carnitine; group 3 was injected with cisplatin; and group 4 was pre-treated with acetyl l-carnitine before cisplatin intraperitoneal injection. According to our results, a significant weight loss was observed in rats from group 3. The thickness of the wall and epithelium of uterine tube were decreased in group 3 rats. We elaborate the protein expression of caspase in epithelium and stroma by IHC. We found that the expression of caspase and the number of TUNEL-positive cells were increased in group 3 rats compared to the other groups. In our study, we showed the protective role of acetyl l-carnitine against uterine tube toxicity caused by cisplatin.

Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats.

BACKGROUND: In this study we investigated the effects of adrenomedullin (AM) and vascular endothelial growth factor (VEGF) on skeletal muscle ischemia/reperfusion (I/R) injury in a rat model. MATERIALS AND METHODS: Thirty-six Wistar rats were randomized into six groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Nothing else was done in Group S (Sham). The Group I/R underwent I/R performed by clamping and declamping of the infrarenal abdominal aorta for 120 min, respectively. Group VEGF and Group AM received intravenous infusion of VEGF (0.8 µg/kg) or AM (12 µg/kg) respectively, without I/R. Group I/R + VEGF and Group I/R + AM received intravenous infusion of VEGF (0.8 µg/kg) or AM (12 µg/kg) immediately after 2 h period of ischemia, respectively. At the end of reperfusion period, skeletal muscle samples of lower extremity were taken from all groups for biochemical and histopathologic examinations. RESULTS: Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and hypoxia inducible factor 1 alpha (HIF 1α) were found to be significantly higher in Group I/R than the levels in Group S (P < 0.05). Tissue levels of MDA, SOD, NO, and HIF 1α were significantly lower in Group I/R + AM compared with the levels in Group I/R (P < 0.05). In Group I/R + VEGF, tissue levels of MDA and NO were significantly lower than the levels in Group I/R (P < 0.05). No statistically significant difference was found in the tissue levels of catalase among the groups. Histologic examination revealed a larger central muscular necrosis than the peripheral necrosis, red blood cells in the lumens of capillary vessels, and a stronger atrophy and elliptical or round shape in muscle fibers in Group I/R. Terminal deoxynucleotidyl transferase mediated dUPT nick end labeling (TUNEL)-positive cell count was significantly lower in groups I/R + AM and I/R + VEGF than Group I/R (P < 0.0001, P < 0.0001, respectively). CONCLUSIONS: These results indicate that AM and VEGF have protective effects on I/R injury in skeletal muscle in a rat model.

Location of proliferating cell nuclear antigen and p53 protein in human first trimester and term placenta.

OBJECTIVE: To examine immunohistochemically the distribution of cell-cycle regulators p53 and proliferating cell nuclear antigen (PCNA), which are in close cooperation with each other in first trimester and term human placentas. STUDY DESIGN: Human first trimester placental tissue was obtained by curettage from legal abortions obtained for social reasons, and human term placental tissue was obtained. Neither the interrupted pregnancy nor the obstetrical history showed any abnormalities. A total of 12 tissue samples were analyzed: n = 6 (6-12 weeks), n = 6 (38-40 weeks). Tissues were evaluated by immunohistochemical study. RESULTS: In the first trimester p53 expression was at a normal level, and p53 immunolabeling was present in syncytiotrophoblast and extravillous trophoblast cells found in the cell column. Very few villous stroma cells were p53 positive. PCNA was present intensely in the cytotrophoblast and in extravillous trophoblast found in the cell column. In term placentas p53 immunolabeling was very low and was expressed in only a limited number of syncytiotrophoblast cells. PCNA was at a normal level in villous and extravillous tissue. PCNA was decreased when compared with the first trimester and was present in syncytiotrophoblast and cytotrophoblast cells. A small number of endothelial cells and villous stromal cells were positive. CONCLUSION: We think that the immunohistochemical distribution of PCNA and p53 are strongly coordinated with each other in villous and extravillous cells in human placenta. This finding may be useful in the explanation of placental pathologies.

The protective effects of acetyl L-carnitine on testis gonadotoxicity induced by Cisplatin in rats.

BACKGROUND: Cisplatin, an effective antineoplastic agent, damages normal cells in a manner related to chemotherapy. Acetyl L-carnitine protects cells against mitochondrial and nuclear damage induced by chemotherapy. AIMS: Animal experiment. STUDY DESIGN: The aim of this study was to examine the protective effects of acetyl L-carnitine on cisplatin-induced gonadotoxicity in testicular structures. Twenty-four male Wistar albino rats were divided into four Groups (n=6): Group 1 (control) was administered saline; Group 2 was administered acetyl L-carnitine; Group 3 was administered cisplatin; and Group 4 was pre-treated with acetyl L-carnitine before cisplatin administration. METHODS: After 72hr of treatment with cisplatin, the rats were sacrificed, and the testicular tissues were removed. Morphometric, histomorphologic and immunohistochemical analyses were conducted. RESULTS: At the end of the experiment, Group 3 was characterised by statistically significant weight loss, a degenerative appearance of the seminiferous tubules in the peripheral region, separation of spermatogenic cell series from the tubular wall, cellular debris in the lumen and central interstitial oedema. Sperm morphology appeared to be abnormal. Tubular diameter and wall thickness decreased, and the number of TUNEL- and active caspase-positive cells increased compared with the other Groups. The histological findings in Group 4 were better than those in Group 3. CONCLUSION: It was concluded that the prophylactic use of acetyl L-carnitine protects against cisplatin-induced testicular tissue damage.