Protective effects of estrogen and bortezomib in kidney tissue of post-menopausal rats: an ultrastructural study.

PURPOSE: Symptoms and disorders related to menopause and its associated estrogen deficiency have become a considerable health concern worldwide. Ovarian hormone depletion/estrogen deficiency can be usefully studied using animal models after removal of the ovaries [ovariectomy (Ovx)]. This study assessed renal changes after Ovx-induced estrogen deficiency in a rat model. METHODS: Rats were randomly allotted into one control group (group I, healthy) and three study groups (group II, Ovx group; group III, Ovx +17ß-estradiol group; and group IV, Ovx + bortezomib group). RESULTS: In the Ovx group (group II), thickening of glomerular capillary walls, narrowing of Bowman's capsular space, glomerular hypertrophy, atrophic tubules, and loss of the basal membranes of the tubules were observed. Mesangial cell proliferation was observed, particularly in the glomerulus. Immunohistochemical (IHC) staining studies in this group showed dense staining in the mesangial cells, tubular cell Nf-KB/p65, and caspase-3. Groups III and IV (Ovx +17ß-estradiol and Ovx + bortezomib) showed decreased NF-kB/p65 and caspase-3 expression compared with the Ovx group (p < 0.05). CONCLUSION: In renal failure related to estrogen deficiency caused by Ovx, 17ß-estradiol and bortezomib have a protective effect on renal tissue.

Effect of mercury vapor inhalation on rat ovary: Stereology and histopathology.

AIM: Mercury, an environmental contaminant, is a risk factor for health in whole living organisms. In this study, we investigated whether mercury vapor (HgO) inhalation has an effect on rat ovary. METHODS: Twelve Wistar albino rats were divided equally into experimental (Hg) and control groups (n = 6). Animals in the Hg group were exposed to HgO for 45 days at a dose 1 mg/m(3)/day, after which, histological and stereological assessment were carried out. RESULTS: Ovaries exposed to HgO had histo-morphometric alterations. HgO inhalation resulted in reduction of the total number of primordial, primary and Graaf follicles. Also, mean volume of ovary, medulla and cortex, corpus luteum (c. luteum) and Graaf follicles was decreased in the Hg group. Moreover, there was a significant increase in total volume of the atretic follicles. On light microscopy, thickening of tunica albuginea, increase of fibrils within the connective tissue, congestion of the capillaries and venous vessels, thinned walls and fibrin deposition in some large blood vessels, and edema were seen. Also, irregular follicle and oocyte borders, and hydropic degeneration in follicular granulosa cells were detected. CONCLUSION: Structural alterations could be attributed to the toxic influence of HgO on rat ovary. The use of Hg should therefore be more controlled to minimize its toxic effect.

Protective effects of beta glucan in brain tissues of post-menopausal rats: a histochemical and ultra-structural study.

Decline of estrogen during menopause has been associated with numerous significant changes that have been linked to many pathophysiological complications. In addition, ovarian hormone deficiency increases the production of reactive oxygen radicals which could result in oxidative stress and cell damage. While estrogen therapy is often considered to overcome the behavioral and physiological shortcomings, antioxidants are gaining popularity for their beneficial property. For this purpose, in the present study, utilizing the antioxidant properties of beta glucan has been examined in treatment of menopause induced oxidative stress in cerebral neurons. Four groups of female Wistar rats were used: control, ovariectomy, ovariectomy + estrogen treated and ovariectomy + beta glucan treated. We observed a significant increase in neural degeneration in ovariectomized rats as compared to controls. Moreover, increased oxidative stress in the brains of the ovariectomized rats has been detected by performing immunohistochemical analysis. A large number of immuno-positive cerebral neurons have been observed in ovariectomy group rat brains. Interestingly, providing beta glucan treatment to ovariectomized rats reduced the number of degenerated neurons. Our study is the first to examine light and electron microscopic examination and immunohistochemical and stereological analysis of estrogen depletion in rats and to test protective role of beta glucan in the experimental study.

Effects of Diabetes on Post-Menopausal Rat Submandibular Glands: A Histopathological and Stereological Examination.

OBJECTIVE: The menopause in elderly women is a physiological process where ovarian and uterine cycles end. Diabetes means higher blood glucose level that is a metabolic disease and has an increased incidence. The aim of the study was to examine the single or combined effects of menopause and diabetes that causes pathophysiological processes on submandibular gland on ovariectomy and diabetes induced rat models. MATERIALS AND METHODS: Sprague Dawley twelve weeks old female (n=24) rats were divided randomly into four groups; Healthy control group (n=6), diabetic group (DM, n=6), ovariectomized group (OVX, n=6), post ovariectomy diabetes induced group (DM+OVX, n=6) individually. Histopathological, histochemical and stereological analyses were done in these groups. RESULTS: Significant neutrophil cell infiltrations and myoepithelial cell proliferations, granular duct and seromucous acini damages and changes in the content of especially seromucous acini secretion in DM and/or OVX groups and distinctive interstitial and striated duct damages in post ovariectomy diabetes induced group were detected. Alterations ingranular ducts hypertrophic and in seromucous acini atrophic were determined in DM and/or OVX groups. CONCLUSION: The results revealed the pathophysiological processes that lead to morphological and functional alterations on the cellular level in submandibular glands. The molecular mechanisms related with pathogenesis of diabetes and menopause need further investigation.

Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced acute liver toxicity in rats.

Paracetamol is one of the first rank drugs which cause hepatic damage during drug intoxications. Endothelin (ET) which is known as one of the most potent vasoactive agent has been shown to contribute in the pathophysiology of various diseases. We hypothesized that bosentan, which is a non-selective ET-1 receptor antagonist, can prevent liver damage. This study included 49 female rats. Groups; I: Healthy group, II: Paracetamol (2 g/kg orally). Groups 3, 4 and 5 received NAC 140 mg/kg (2 doses), BOS 45 mg/kg and BOS 90 mg/kg orally, respectively. 1 h after administration of pretreatment drugs, Groups 3, 4, 5 were given paracetamol. VI: received BOS 90 mg/kg. VII: received 140 mg/kg NAC (2 doses). According to biochemical results, TNF-α, ALT and AST levels were statistically increased in the paracetamol group, these parameters were improved in the bosentan groups. Paracetamol administration decreased SOD activity, GSH level and increased level of MDA in the liver, while bosentan administration significantly improved these parameters. In immunohistochemical staining ET-1 receptor expression was excessively increased in paracetamol group, but not in bosentan groups when compared to healthy control. All these results suggest that bosentan exerted protective effects against experimentally induced paracetamol toxicity in liver.

A new hypothesis about hematopoietic Pbx-interaction protein (HPIP): can it be a key factor in neurodegeneration in the post-menopausal period?

Neuronal degeneration in the post-menopausal term leads to cognitive symptoms such as anxiety, difficulty in concentrating, overreacting to minor upsets, quickly becoming irritated and forgetfulness in approximately 70-80% of all women around the world. These symptoms, which result from microtubule damage in the axon extensions of hippocampal neurons in during menopause, greatly reduce individuals' life quality. Thus, an investigation of the estrogen receptor-signaling pathway-microtubule dynamic triangle and the possible links between them is important when it comes to explaining the possible mechanism of neurodegeneration. Hematopoietic Pbx-interaction protein (HPIP), a microtubule-binding protein, is a novel scaffolding protein. The detection of this protein on neurons represents the most important step in our hypothesis. The importance of the hypothesis is that it might provide important clues about the possible role of HPIP and its mechanism through in vivo and in vitro studies of estrogen receptors-microtubules and the HPIP triangle in terms of neuronal degeneration in the post-menopausal period. A preliminary study was performed to test the main part of our hypothesis using real-time PCR. According to the results, the mRNA expression of HPIP was found in hippocampal neurons. After the detection of this novel protein in neurons, it was observed that there were differences in the experimental groups when compared with the control group relating to the mRNA expression of this protein. An important scientific question remains concerning the mechanisms of neurodegeneration appearing in the post-menopausal period and the receptors, proteins, and signaling pathways that play a role in this degeneration. In consideration of the data from in vivo and in vitro studies used to test our hypothesis, we will try to address the relevant questions. As this issue is resolved, new studies and treatment procedures that can help to prevent the possible difficulties in the menopausal period will be illuminated.

The role of infliximab on paracetamol-induced hepatotoxicity in rats.

Paracetamol has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Infliximab is tumor necrosis factor alpha (TNF-α) inhibitor agent, which has been developed as a therapeutic agent for TNF-α-mediated disease. It acts by binding and neutralizing TNF. The aim of our study was to evaluate the hepatoprotective activity of infliximab on paracetamol-induced hepatotoxicity and to understand the relationship between the TNF-α and paracetamol-induced liver injury. Fifty-six rats were divided into eight groups as each composed of seven rats: (1) intact, (2) 7 mg/kg infliximab, (3) 140 mg/kg NAC, (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 3 mg/kg infliximab, (7) 2 g/kg paracetamol + 5 mg/kg infliximab and (8) 2 g/kg paracetamol + 7 mg/kg infliximab groups. Liver function tests including lipid peroxidation levels were analyzed and histopathological changes of liver were also observed. There were statistically significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), levels of TNF-α and malondialdehyde (MDA) and decreases in the activity of superoxide dismutase (SOD) and level of glutathione (GSH) in the group treated with paracetamol. Infliximab administration dramatically reduced serum ALT, AST and TNF-α level. Also, it restored GSH, SOD and decreased MDA levels in liver. Liver histopathological examination showed that infliximab administration antagonized paracetamol-induced liver pathological damage. The results of present study suggest that infliximab has significant hepatoprotective activity on paracetamol-induced hepatotoxicity.

Stereological evaluation of the kidneys of anencephalic and normal fetuses.

The aim of this study is to test the glomerular and other quantitative parameters of kidneys of anencephalic fetuses and comparing those to "normal" fetuses. In this study, 20 kidneys of human fetuses (5 boys and 5 girls of anencephalic fetus, and 5 boys and 5 girls of normal fetus), at gestational ages of 25-30 weeks, were examined. This study is based on two basic research methods: one is a conventional anatomical measurement at the macroscopical level; the other is a design-biased stereological method at the microscopical level. Physical dissector and Cavalieri principle were used to estimate the total and numerical density of glomerulus and the volume of kidney, respectively. The results of the two types of investigation were compared based on anencephalic/normal and boy/girl kidneys at both the macroscopical and microscopical levels. There was no significant difference found between the quantitative features of kidneys (volume of kidneys and mean number and/or height of glomerulus) belonging to anencephalic and normal fetuses. The results of this study suggest that anencephalic fetuses did not differ from normal fetuses in respect of kidneys.

Bilateral ovariectomy in young rats: what happens in their livers during cecal ligation and puncture induced sepsis?

STUDY OBJECTIVE: Pediatric ovarian masses comprise a heterogeneous group of benign and malignant lesions. Surgical methods consist of emergency or programmed surgery with tumoral resection and uni/bilateral oophorectomy or salpingo-oophorectomy. We examined whether bilateral ovariectomy (OVX) worsens liver injury during the onset of cecal ligation and puncture (CLP)-induced sepsis in rats. DESIGN: The rat groups were: sham, bilateral-OVX, sepsis, and OVX-sepsis. SETTINGS: After OVX operation, rats were allowed to recover for 12 weeks. At the end of recovery, CLP was applied 16 hours after sepsis induction. MAIN OUTCOME: There was a significant difference in the numerical density of hepatocytes only between the sepsis and the OVX-sepsis groups. Serum ALT and AST were increased significantly in the OVX-sepsis group. NF-κB activation after OVX increased after induction of sepsis. OVX-sepsis group showed marked thrombosis in portal vein branches and the central vein, degeneration in the bile ducts, and widespread ischemic areas in liver sections. Intra-inflammatory cell invasion was observed in both the portal and intrasinusoidal areas. DISCUSSION: This study indicates that increases in liver NF-κB activity in ovariectomized rats following CLP-induced sepsis correlates with elevated levels of serum ALT and AST and with histopathologic changes in rat liver. Bilateral OVX therefore appears to play a role in the activation of NF-κB or in production of cytokines in liver cells. Thus, we provided novel insight into the effects of OVX on liver injury following CLP-induced sepsis.

Chronic treatment of haloperidol induces pathological changes in striatal neurons of guinea pigs: a light and electron microscopical study.

In the present work, we investigated whether there would be any change in histological structure of striatal neurons after haloperidol applications at different doses. Adult male guinea pigs were treated once-daily with saline (group 4, control) or haloperidol during 6 weeks, and the dose was 1, 2, or 3 mg/kg (groups 1, 2, and 3, respectively). After treatment, all animals were anesthetized and striata were dissected and examined. When striata were evaluated histologically, dark neurons and some degenerating striatal neurons had distinctive morphological changes consistent with cell death, including reduced neuronal size with nuclear and cytoplasmic shrinkage. Also, in sections of striata in groups 1 and 2, but not in group 3, more glial cells were observed than in those of the control group. In all treated groups, fibrous content of intersititium was paralelly increased by increasing dose. Ultrastructural investigation of striatal neurons in haloperidol-treated rats showed notched nuclei and many lysosomes. Moreover, degeneration of myelin, scarce microglial macrophages, expansion of nuclear intermembranous space, degenerated mitochondria, and vacuoles were found. Also, cytoplasmic swelling, lysosomes, and apoptotic bodies were present. These results suggest that haloperidol treatment may lead to damage in neurons via the necrotic process in both low- and high-dose applications.

Comparing effects of lacidipine, ramipril, and valsartan against experimentally induced myocardial infarcted rats.

In this study, the effects of lacidipine (LAC), ramipril (RAM), and valsartan (VAL) on biochemical and histopathologic changes in heart tissue were studied in rats with isoproterenol-induced (ISO-induced) myocardial infarction (MI). LAC, RAM, and VAL had been administered via oral gavage at 3, 3, and 30 mg/kg doses, respectively, once per day during a 30-day time period. On days 29 and 30, the drug treatment group and the control group (with the exception of the intact control group, in which no medications were given, and ISO was not administered) were administered 180 mg/kg ISO subcutaneously over an interval of 24 h. After this period, the hearts of the rats were removed and processed for biochemical and histopathologic studies. The antioxidant parameters superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were estimated. A diagnosis of MI was confirmed with antioxidant parameters and histopathologic findings. In MI control groups, histopathologic indicators were found to be statistically higher than those in drug groups; an increase in histopathologic indicators of MI correlates with significant decreases in SOD and CAT levels, and an increase in MDA level. Histopathologic grades of MI indicators were significantly higher in MI group that did not receive any cardioprotective medications in comparison with MI groups that received LAC, RAM, and VAL. Each of the three medications favorably modulated most of the biochemical and histopathologic parameters observed. No significant difference existed with regard to any of the estimated parameters in the rat groups that received medications without MI induction. In conclusion, results indicate that LAC, RAM, and VAL significantly reduced myocardial injury and emphasize the cardioprotective nature of these agents.

A new hypothesis about neuronal degeneration appeared after a rat model of menopause.

OBJECTIVE: Estrogen is suggested to be one of the most important regulators of neuronal function, including neuronal proliferation, survival and plasticity. There is a broad consensus that the loss of ovarian hormones is associated with neurodegeneration in the hippocampus that leads to cognitive impairment. METHODS: A total of 8 female rats which were subjected to bilateral ovariectomy were included in this study. After ovariectomy, the rats were housed for 123 days in a standard laboratory. At the end of the 123 days, the rats were euthanized and the brain sections were investigated by conventional light microscopic and electron microscopic techniques. RESULTS: The regular structure of almost all axon extensions was lost. The majority of these extensions had a sawtooth-like appearance in longitudinal section profiles. Especially in transfer section profiles of myelinated axons, some morphological changes were shown which may be matched up with light microscopic findings. CONCLUSIONS: Deficiency of estrogen will initially affect microtubule organization. When this organization breaks down, it will physically cause the distribution of the normal structure of axonal plasmalemma. This in turn will lead to the distribution of physical organizations of estrogen and other different types of receptors which are placed in both the membrane and microtubules in the axon.

The effects of testosterone on intestinal ischemia/reperfusion in rats.

ABSTRACT Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.

Effects of diabetes mellitus on the rat liver during the postmenopausal period.

The present study investigated whether diabetes worsened the onset of liver injury/damage during the ovariectomized (OVX)-induced postmenopausal period in rats. Diabetes results in severe complications in humans, such as liver failure. Estrogen and its derivatives are medically acceptable, powerful antioxidant agents that can enable liver and other important organs to defend themselves against oxidative related injury. Estrogen deficiency, which occurs in the postmenopausal period and in individuals with diabetes, may play a significant role in the progression of liver failure. In the present study, rats were divided into four groups: control (Group I), diabetic (Group II), ovariectomy (Group III) and ovariectomy plus diabetes (Group IV). After the experiments, quantitative histopathological and immunohistochemical changes in liver were detected using light microscopy and modern stereological systems. Histopathological examinations showed that there were many necrotic and apoptotic hepatocytes in the lobules of Group II. In addition, there were a larger number of necrotic cells in Group III than Group II. In contrast to Group II, there were also apoptotic cells in the portal areas in Group III. Moreover, evidence of liver injury was higher in the sections of Group IV compared with all other groups. In biochemical findings, there were statistically significant differences between all the groups (P < 0.001) for catalase (CAT), glutathione peroxidase (GSH) and myeloperoxidase (MPx) activity. In addition, the amount of lipid peroxidation (LPO) was significantly different between groups. In stereological results, there were significant differences between Groups I and II and Groups II and IV. The present study provided novel insight into the pernicious effects of ovariectomy on liver injury following the onset of diabetes. Indeed, the present study found that increases in liver oxidative activity in OVX rats following the onset of diabetes correlates with elevated MPx, LPO and histopathological changes in rat liver.

The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity.

This study was designed to investigate the qualitative and quantitative changes in brain tissue following aluminum chloride (AlCl(3)) administration and to determine whether boric acid (BA) has a protective effect against brain damage induced by AlCl( 3). For this aim, Sprague-Dawley rats were randomly separated into eight groups: (1) control, (2) AlCl(3) (5 mg/kg/day), (3, 4 and 5) BA (3.25, 36 and 58.5 mg/kg/day), (6, 7 and 8) AlCl(3) (5 mg/kg/day) plus BA (3.25, 36 and 58.5 mg/kg/day). After the animals were killed, the total numbers of neuron in the brain of all groups were determined using an unbiased stereological analysis. In addition to the stereological analysis, all brains were examined histopathologically by using light and electron microscopy. The stereological and histopathological results indicated a high damage of the rat brain tissues in the AlCl(3) and AlCl(3) + high dose BA (36 and 58.5) treatment groups. However, protective effects on neuron were observed in the AlCl(3) + low dose BA (3.25) group when compared other AlCl(3) groups. Our stereological and histopathological findings show that low-dose BA, as a proteasome inhibitor, can decrease the adverse effects of AlCl(3) on the cerebral cortex.

Effects of haloperidol on striatal neurons: relation to neuronal loss (a stereological study).

In the present work, we investigated the effect of chronic haloperidol administration on the number of striatal neurons in guinea pigs. For this purpose, adult male guinea pigs were given daily injections of 1, 2 or 3 mg/kg of haloperidol for 6 weeks. After treatment, the animals were anesthetized via brief inhalation of ether, the brains were removed and the corpus striatum was dissected. Then the tissues were processed and semi-thin sections were stained with toluidine blue for stereological and histopathological evaluation. The physical disector was used for measurements of nuclear height and numerical density of striatal neurons and also to evaluate both normal and degenerated neurons within the corpus striatum of treated animals and untreated controls. In the control group, the mean numerical density of neurons was calculated as 47.92 cell/mm3 and the mean nuclear height as 3.58 µm. Mean densities of all (both viable and degenerated) neurons were calculated to be 45.46 in the low-dose (p < 0.01), 39.73 in the medium-dose (p < 0.001) and 30.31 cell/mm3 in the high-dose group (p < 0.001). Mean densities of degenerated neurons in the low, medium and high dose group were 30.72, 22.93 (p < 0.001) and 15.56 cell/mm3 (p < 0.001) respectively. Mean nuclear heights were 2.804 (p < 0.0001), 2.78 (p < 0.0001) and 2.33 µm (p < 0.00001) in the low, medium and high dose group, respectively.

Growth hormone reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.

OBJECTIVE: To evaluate the effects of growth hormone (GH) as an antioxidant and tissue-protective agent and analyse the biochemical and histopathological changes in rat ovaries due to experimental ischemia and ischemia/reperfusion injury. STUDY DESIGN: Forty-eight adult female rats were randomly divided into eight groups. In Group 1, a period of bilateral ovarian ischemia was applied. In Groups 2 and 3, 1 and 2 mg/kg of GH was administered, and 30 min later, bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). Group 4 received a 3-h period of ischemia followed by 3h of reperfusion. Groups 5 and 6 received 1 and 2 mg/kg of GH, respectively, 2.5 h after the induction of ischemia. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3h of reperfusion continued. Group 7 received a sham operation plus 2mg/kg of GH. Group 8 received a sham operation only. After the experiments, superoxide dismutase and myeloperoxidase activity and levels of glutathione and lipid peroxidation were determined, and histopathological changes were examined in all rat ovarian tissue. RESULTS: Ischemia and ischemia/reperfusion decreased superoxide dismutase activity and glutathione levels in ovarian tissue, but increased lipid peroxidation levels and myeloperoxidase activity significantly in comparison to the sham group. The 1 and 2 mg/kg doses of GH before ischemia and ischemia/reperfusion decreased lipid peroxidation levels and myeloperoxidase activity in the experimental groups. The administration of GH before ischemia and ischemia/reperfusion treatments also increased superoxide dismutase and glutathione levels. The histopathological findings also suggested a protective role of GH in ischemia/reperfusion injury. That is, ovarian tissues in the ischemia groups showed histopathological changes, such as haemorrhage, cell degeneration, and necrotic and apoptotic cells, but these changes in the GH groups were lesser. Moreover, in the ischemia/reperfusion groups, acute inflammatory processes--such as neutrophil adhesion and migration, apoptotic and degenerative cells, stromal oedema and haemorrhage--were present. However, the ovarian tissues of the IR+GH (1 mg) group had minimal apoptotic cells, and the IR+GH (2 mg) group had no apoptotic cells. In addition, the general ovarian histological structures of these groups were similar to those of the healthy control group. CONCLUSIONS: The administration of GH is protective against ischemia and/or ischemia/reperfusion-induced ovarian damage. This protective effect can be attributed to the antioxidant properties of GH.

Protective effects of montelukast on ischemia-reperfusion injury in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.

OBJECTIVE: To reveal the effects of montelukast as an antioxidant and tissue protective agent and study the biochemical and histopathologic changes in experimental ischemia and ischemia-reperfusion (I/R) injury in rat ovaries. DESIGN: Experimental study. SETTING: Experimental surgery laboratory in a university department. ANIMAL(S): Forty-eight rats with experimentally induced ovarian torsion. INTERVENTION(S): Group 1: sham; Group 2: ovarian ischemia; Group 3: a 30-hour period of ischemia followed by a 3-hour reperfusion. Groups 4 and 5: rats administered 10 and 20 mg/kg doses of montelukast before a half-hour of ischemia, then ovarian ischemia applied; after a 3-hour period of ischemia, the bilateral ovaries removed. Groups 6 and 7: 3-hour period of ovarian ischemia applied, then 2.5 hours after the ischemia induction, rats given montelukast. Group 8: sham operation and 20 mg/kg of montelukast; at the end of a 3-hour period of ischemia, 3-hours of reperfusion continued. MAIN OUTCOME MEASURE(S): Measurement of ovarian tissue concentrations of superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO) and myeloperoxidase (MPO) activity; and histopathologic examination of all ovarian rat tissue. RESULT(S): Montelukast treatment normalized changes of LPO and MPO and stimulated an overproduction of endogenous SOD and GSH. The results of the histologic parameters showed that treatment with montelukast in the I/R group of rats ameliorated the development of ischemia and reperfusion tissue injury. CONCLUSION(S): Montelukast at different doses attenuates ovarian I/R-induced ovary tissue injury in rats.

The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats.

OBJECTIVES: Sepsis model was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or concomitantly, on the response of the activity of the nuclear factor kappa B (NF-kappaB) and the oxidative response in kidney. SUBJECTS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Diabetes was induced in female rats using administration of alloxan. The rats were divided into five groups: sham control (group 1), ovariectomy (group 2), ovariectomy + sepsis (group 3), ovariectomy + diabetes (group 4), and ovariectomy + diabetic + sepsis (group 5). RESULTS: In kidney tissues, the levels of lipid peroxidation (LPO) and glutathione (GSH) and the activity of catalase (CAT) were higher for groups 3, 4, 5 than the control groups. Superoxide dismutase (SOD) activity was lower for groups 3, 4, 5 than the control groups. We determined that CLP produced injury evident in the kidneys of rats when compared to the control group, whereas the severity of the injury was higher in the diabetes + ovariectomy + CLP group when compared to the CLP group. In immunohistochemical staining, we determined that CLP operation increased NF-kappaB activation. In the ovariectomized, septic, and diabetic group, NF-kappaB activation was significantly higher than other groups. CONCLUSIONS: Hyperglycemia and ovariectomy severely increased NF-kappaB activation and oxidant levels with the stages of our sepsis model. Ovariectomy resulted in general changes in metabolism, which are seen in the kidney with diabetes under sepsis conditions.

Atorvastatin reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.

The aim of this study was to evaluate the effects of atorvastatin as an antioxidant and tissue protective agent and study the biochemical and histopathological changes in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. The experiment used 48 adult female rats, and the experimental groups can be summarized as: group I, a sham operation; group II, a sham operation +10 mg/kg atorvastatin; group III, bilateral ovarian ischemia; and groups IV and V, bilateral ovarian ischemia +5 and 10 mg/kg atorvastatin before 30 min of ischemia, respectively (after a 3-h period of ischemia, the bilateral ovaries were surgically removed); group VI, 3-h period of ischemia followed by 3-h reperfusion; groups VII and VIII received 5 and 10 mg/kg atorvastatin, respectively, 2.5 h after the induction of ischemia, and at the end of a 3-h period of ischemia, bilateral vascular clips were removed and 3-h reperfusion continued. After the experiments, superoxide dismutase (SOD) and myeloperoxidase (MPO) activity and levels of glutathione (GSH) and lipid peroxidation (LPO) were determined, and histopathological changes were examined in all rat ovarian tissue. Ischemia and I/R increased the LPO level and MPO activity while decreasing the SOD activity and GSH level significantly in comparison to the sham group. The 5- and 10-mg/kg doses of atorvastatin before ischemia and I/R reversed the trend in LPO level and MPO activity. The levels of SOD and GSH were decreased by ischemia and I/R. The administration of atorvastatin before ischemia and I/R treatments also reversed the trend in the SOD and GSH levels. In the I/R plus atorvastatin groups, although minimal vascular dilation in the ovary stoma and some degenerative cell clusters were seen, most of the cellular structures showed no pathological changes. Administration of atorvastatin is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.