Biological and histopathological investigations of moclobemide on injured ovarian tissue following induction of ischemia-reperfusion in rats (original) (raw)
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Journal of pediatric surgery, 2015
The purpose of the study is to evaluate the effect of vardenafil on the histopathology and biochemical parameters in reducing damage in experimental ovarian ischemia and ischemia/reperfusion injury in a rat model and to compare the effect of two different doses of vardenafil. Forty-two rats with experimental ovarian torsion. Group-I: sham; Group-II: ovarian ischemia; Group-III: 2 hours of ischemia followed by a 2-hour reperfusion. Group-IV: two hours before the sham operation, rats received 1mg/kg vardenafil; Group V and VI: A 2-hour period of ovarian ischemia was applied, in which rats were treated with intraperitoneal vardenafil 1 and 2mg/kg dose, after 1.5hours of ovarian ischemia. After 2hours of reperfusion, the ovaries on the right side were removed for examination. The ovarian ischemia/reperfusion injury was evaluated by calculating total antioxidant status, total oxidant status and oxidative stress index; and histopathologic examination of all ovarian rat tissue. The histolo...
Protective effect of vardenafil on ischemia–reperfusion injury in rat ovary
TURKISH JOURNAL OF MEDICAL SCIENCES, 2013
Introduction Ovarian torsion is a serious gynecologic emergency condition. Although it might affect all women, it is usually seen in women of reproductive age (1). Ovarian ischemia is the result of torsion and leads to cell death because of insufficient perfusion of the tissue (2,3). Ischemic tissues need to recover blood supply for regeneration of cells and disposal of toxic metabolites. However, reperfusion of the ischemic tissue paradoxically leads to much more serious damage to the tissue than the damage caused by ischemia (4). The ischemia and reperfusion injuries are related to the production of reactive oxygen species (ROS) (5). Ischemiareperfusion (I/R) injury increases the production of free radicals such as ROS and malondialdehyde (MDA). Activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) increase to protect the ischemic tissue from the harmful effects of toxic metabolites (3). Free oxygen species result in oxidative injury via different mechanisms, such as metabolic dysfunction or impairment of calcium intracellular homeostasis. They may lead to cell injury or cell death by themselves or by deactivating various enzymes (6). Extreme production of ROS causes alterations in subcellular structures. These changes are modifications of protein and DNA, lipid peroxidation (LPO) of polyunsaturated fatty acids in membranes (7), apoptosis (8), and depression of cellular antioxidant system (9). MDA is the end product of LPO, and thus increased MDA content is an important indicator of LPO (10). Cells have different mechanisms against oxidative damage. These mechanisms involve enzymatic and nonenzymatic defense systems. SOD, CAT, and GPx are included in enzymatic defense systems (11). If the cells do not have enough antioxidant enzymatic activity, ROS levels increase. Apoptosis protease-activating factor 1 (Apaf-1), an important part of apoptosome, is a protein that plays a central role in apoptosis (12). When apoptosis is stimulated, Apaf-1 binds cytochrome c and procaspase 9, and then caspase-3 and-7 become activated. This complex is called apoptosome and results in the loss of the cell (13). Cellular stresses, such as hypoxia, lead to caspase activation. This process results in apoptotic cell death (12). Aim: To investigate the effect of vardenafil on ischemia-reperfusion (I/R) injury in rat ovary. Materials and methods: A total of 21 Wistar rats were divided into 3 groups. In group 1, ovary torsion was not performed and no drug was administered. In group 2, 1 h of ischemia and 2 h of reperfusion were performed and no drug was given. In group 3, 1 h of ischemia and 2 h of reperfusion were performed and 1 mg/kg vardenafil was administered after 30 min of ischemia. Right ovaries were surgically removed in all groups. Malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. Apoptosis protease-activating factor 1 (Apaf-1) was measured by using immunohistochemistry. Results: MDA level was significantly increased and SOD, CAT, and GPx activities were significantly decreased in group 2 compared to the other groups (P < 0.05). In light microscopic investigations, severe vascular congestion, edema, hemorrhage, and follicular degeneration were assessed in the ovary tissue. Ovarian tissue damage was higher in group 2 than group 3. Apaf-1 expression was stronger in group 2 than group 3. Conclusion: Vardenafil treatment seems to reduce microscopic histopathological changes, decrease Apaf-1 response, and alter oxidative stress in I/R injury in rat ovaries.
Zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary
Journal of Obstetrics and Gynaecology Research, 2014
The aim of the study was to investigate the effectiveness of zofenopril in an experimental model of ovarian torsion in rats with histologic and biochemical assessments. Material and Methods: Experimental procedures were performed on 35 female rats (Wistar albino). Rats were randomly divided into five groups as: sham (sham operated, n = 7); vehicle group 1 (torsion-detorsion, n = 7) with 2 h ischemia and 2 h reperfusion; vehicle group 2 (torsion-detorsion, n = 7) with 2 h ischemia and 5 days' reperfusion; zofenopril group 1 (torsion-detorsion, n = 7) with 2 h ischemia, 2 h reperfusion and a signal dose of oral 15 mg/kg zofenopril; and zofenopril group 2 (torsion-detorsion, n = 7) with 2 h ischemia, 5 days' reperfusion and 5 days' oral 15 mg/kg zofenopril. A scoring of histopathologic evaluation was performed on the ovaries according to congestion, bleeding, edema, and cellular degeneration. Biochemical assessments included catalase, tissue malondialdehyde and protein carbonyl. Results: Compared with the vehicle groups, histopathologic scores, tissue malondialdehyde and protein carbonyl levels, which reflect oxidative stress markers, were significantly lower in the zofenopril groups. Furthermore, catalase levels were significantly increased in the zofenopril group. Conclusion: Our study results revealed that zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary.
Attenuation of Ischemia/Reperfusion-Induced Ovarian Damage in Rats: Does Edaravone Offer Protection
European Surgical Research, 2013
Aim: The aim of this study was to investigate whether prophylactic treatment with edaravone prevents ischemia/reperfusion (I/R)-induced ovarian damage during pneumoperitoneum in an experimental rat model. Methods: Twenty-eight female Sprague Dawley rats were allocated randomly to 4 groups. The sham group (group 1) was only subjected to catheter insertion, not to pneumoperitoneum. Group 2 received a 1 mg/kg dose of 0.9% sodium chloride by the intraperitoneal route for 10 min before pneumoperitoneum. Groups 3 and 4 received 6 and 12 mg/kg edaravone, respectively, by the intraperitoneal route for 10 min before pneumoperitoneum. After 60 min of pneumoperitoneum, the gas was deflated. Immediately after the reperfusion period, both ovaries were excised for histological scoring, caspase-3 immunohistochemistry and biochemical evaluation including glutathione (GSH) and malondialdehyde (MDA) levels. Also, total antioxidant capacity (TAC) was measured in plasma samples to evaluate the antioxidant effect of edaravone. Results: Ovarian sections in the saline group revealed higher scores for follicular degeneration and edema (p < 0.0001) when compared with the sham group. Administration of different doses of edaravone in rats significantly prevented degenerative changes in the ovary (p < 0.0001). Caspase-3 expression was only detected in the ovarian surface epithelium in all groups, and there was a significant difference between the treatment groups and the saline group (p < 0.0001). Treatment of rats with edaravone reduced caspase-3 expression in a dose-dependent manner. Moreover, biochemical measurements of oxidative stress markers (MDA, GSH and TAC) revealed that prophylactic edaravone treatment attenuated oxidative stress induced by I/R injury. Conclusion: These results indicate that prophylactic treatment with edaravone prevents I/R-induced ovarian damage during pneumoperitoneum in an experimental rat model. Also, we evaluated the effect of various doses of edaravone on these parameters. In the light of present and previous reports, we can propose that edaravone may have beneficial effects on ovarian I/R injury through its antioxidant and free radical scavenging properties. The absence of long-term alterations of both biochemical and histological parameters is another limitation of our study. Long-term results may give us more detailed information about the relationship between ovarian damage and laparoscopy-related I/R injury.
Effects of iloprost on experimental ischemia and reperfusion injury in rat ovary
Biotechnic & Histochemistry, 2020
We investigated the protective effect of iloprost against ischemia/reperfusion (I/R) injury in rat ovary. We used 32 female Sprague-Dawley rats randomly allocated to four experimental groups: sham, ischemia, I/R and I/R + iloprost. Ovarian torsion was established in all rats except the sham group. The torsion group was exposed to ischemia for 3 h. The detorsion group was exposed to 3 h ischemia applied + 3 h reperfusion. The detorsion + iloprost group was exposed to ischemia for 3 h + reperfusion for 3 h + intravenous (IV) iloprost infusion for 60 min starting at the beginning of reperfusion. Ovaries were removed and prepared for histopathological evaluation. Reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the blood. The total histopathological injury score and MDA level of the ischemia group were significantly higher than for the sham group. Ovarian injury score and MDA level following I/R increased compared to the ischemia group. Iloprost administration reduced the total injury score and MDA level. The GSH level was higher in the I/R + iloprost group than in the I/R group. We concluded that IV iloprost administration reduces I/R injury in rat ovarian tissue.
ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY, 2020
Objective: Ovarian torsion is a gynecologic problem that presents as acute lower abdominal pain. As a result, blood flow to the ovaries decreases and ischemia develops. Many medications have been used to treat ovarian torsion, including carvacrol. We conducted an experimental ischemia/reperfusion (torsion-detorsion) model using rats to observe the effects of carvacrol on ovarian torsion by immunohistochemical study. Study Design: Thirty-two female Wistar rats were randomly categorized into 4 groups (8 rats per group): control group, ischemia group, ischemia/reperfusion group, and ischemia/reperfusion+carvacrol–treated group. Ischemia was created by sealing the left ovaries for 3 hours, followed by 3-hour reperfusion. For the ischemia/reperfusion+carvacrol–treated group, 100 mg/kg carvacrol was administered orally in 2 mL 0.9% NaCl after the reperfusion. All animals were sacrificed, and ovarian tissues were dissected for routine paraffin wax embedding tissue protocol. Results: Control groups showed normal ovarian histological structures. In the ischemia group, hyperplastic granulosa cell vascular dilation, severe hemorrhage, and inflammation were observed. The ischemia/reperfusion group showed edema, inflammation, congestion, degenerated follicles, and cells with pyknotic nuclei. In the ischemia/reperfusion+carvacrol group, degenerative changes and vascular pathologies were decreased in ovarian tissues. Endothelin-1 (ET-1) was expressed in degenerated follicles and vascular endothelial cells in the ischemia and ischemia/reperfusion group. Expres-sion of ET-1 was decreased in follicular cells but negative in stromal and luteal cells in the ischemia/reperfusion+carvacrol group. ADAMTS-5 expression was positive in degenerated follicles, apoptotic cells, and inflammatory cells in the ischemia and ischemia/reperfusion groups. In the ischemia/reperfusion+carvacrol group, corona cells and a few inflammatory cells around vessels showed positive ADAMTS-5 expression. Conclusion: ET-1 can induce angiogenic development with the decrease of degenerative development and inflammation in the carvacrol group. ADAMTS-5 molecule may be a marker of cellular structure and extracellular matrix development in different stages of development of ovarian cells and follicles in ischemia and oxygen deficiency caused by ischemia reperfusion.
Medical Science and Discovery, 2020
In this study, the effectiveness of caffeic acid phenethyl ester (CAPE) and Dehydroepiandrosterone (DHEA) in preventing ischemia reperfusion injury associated with ovarian torsion have been investigated. Materials and Methods: Twenty four adult female Wistar Albino rats were randomly divided into four groups. Ovaries were not twisted, and only healthy ovarian tissues were removed from the rats in the first group, while ovaries were twisted for 3 hours in the other groups. The second group did not receive any medications before the ovaries were untwisted, while 20 micromole/kg of CAPE was applied on peritoneal surface to the third group, and 60 mg/kg of DHEA was administered intraperitoneally to the fourth group. Results: The level of primordial follicles was higher in the third group compared to the second group after the torsion of the ovary (p=0.017). The mean level of primary follicles was higher in the first group compared to the number of follicles in the third and fourth groups after the torsion of the ovary (p<0.001). The median hemorrhage level was higher in the second group following ovarian torsion compared to that in the first group (p=0.005). Conclusion: Agents that have been considered to reduce injury resulting from ischemia-reperfusion proved ineffective during the early stages in terms of the number of follicles in the ovaries; however, we believe that long-term studies may be more beneficial.