Osman Nuri Keles

Protective effects of amlodipine on ischemia-reperfusion injury of rat ovary: biochemical and histopathologic evaluation

OBJECTIVE To evaluate the effects of telmisartan as an antioxidant and for its tissue protective properties and to study the biochemical and histopathologic changes in experimental ischemia and ischemia/reperfusion injuries in rat ovaries. DESIGN Experimental study. SETTING Experimental surgery laboratory in a university department. ANIMAL(S) Forty-eight female adult rats. INTERVENTION(S) I: sham operation; II: bilateral ovarian ischemia; III: 3 h ischemia + 3 h reperfusion. IV and V: Rats were administered 10 and 20 mg/kg doses of telmisartan, respectively, before 0.5 h of ischemia, and then ovarian ischemia was applied; after 3 h of ischemia, the ovaries were removed. VI and VII: 3 h ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of telmisartan; at the end of 3 h of ischemia, the ovaries were removed and a 3 h reperfusion followed. MAIN OUTCOME MEASURE(S) Superoxide dismutase, inducible nitric oxide synthase, and myeloperoxidase activity in rat ovarian tissue; and histopathologic changes in the ovarian tissue of the rats. RESULT(S) Ischemia and ischemia-reperfusion increased the inducible nitric oxide synthase and myeloperoxidase activity while decreasing the super oxide dismutase activity significantly in comparison with the sham group. Before ischemia and ischemia/reperfusion, telmisartan reversed the trend in inducible nitric oxide synthase activities and the level of myeloperoxidase. CONCLUSION(S) telmisartan is effective in reversing tissue damage induced by ischemia/reperfusion in ovaries.

Spirulina platensis feeding inhibited the anemia- and leucopenia-induced lead and cadmium in rats

In the present investigation, the effect of Spirulina platensis (Sp) was undertaken on rats fed with lead and cadmium including diet by using physiological, enzymehistochemical and stereological methods. For this aim, 50 rats were equally divided into five groups as control (C), lead (Pb), Spirulina+lead (Sp+Pb), cadmium (Cd), and Spirulina+cadmium (Sp+Cd). Red blood cell (RBC) and white blood cell (WBC) counts, packed cell volume (PCV), and haemoglobine (Hb) concentrations were determined by haemocytometric methods in blood samples collected on 30th day. Population of T lymphocyte was counted by the alpha-naphthyl acetate esterase (ANAE) staining method, and reticulocytes were counted by stereological method. The counts of RBC, WBC, and ANAE positive T lymphocyte, and the values of Hb, PCV, and MCHC were decreased in the Pb and Cd groups compared to control group. Also, the number of reticulocytes (polychromatofilic erythrocyte) increased in the Pb groups, whereas it decreased in the Cd group. On the other hand, these values were ceased by S. platensis in the treated groups. These results suggest that S. platensis supplementation may be useful in adjuvant treatment of leukemia and anemia caused by lead and cadmium toxication.

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.

Protective effects of erythropoietin on ischemia/reperfusion injury of rat ovary

OBJECTIVES To evaluate the effects of erythropoietin (EPO) 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. STUDY DESIGN 36 Adult female rats were used. The experimental groups were designed as Group 1: sham operation; Group 2: bilateral ovarian ischemia; and Group 3: 3 h period of ischemia followed by 3 h reperfusion. Group 4 rats were administered a 5000 IU dose of EPO, before 0.5 h of ischemia, and then bilateral ovarian ischemia was applied. After a 3 h period of ischemia, the bilateral ovaries were removed. In Group 5, a 3 h period of bilateral ovarian ischemia was applied. 2.5 h after the induction of ischemia, the rats were administered the same dose of EPO. At the end of a 3 h period of ischemia, 3h reperfusion was continued after the ovaries were removed. Group 6 underwent a sham operation after administration of 5000 IU/kg of EPO. After the experiments, superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and myeloperoxidase (MPO) activity were determined, and histopathological changes were examined in all rat ovarian tissue. RESULTS Ischemia and ischemia/reperfusion increased the iNOS and MPO activity while decreasing the SOD activity significantly in comparison to the sham group. The 5000 IU/kg of EPO before ischemia and I/R reversed the trend in iNOS and MPO activities. The levels of SOD were decreased by the ischemia and I/R. The administration of EPO before ischemia and I/R treatments also reversed the trend in the SOD levels. In the ischemia/reperfusion plus EPO groups, though we observed minimal vascular dilation in the ovary stroma and some degenerative cell clusters, most of cellular structures did not show any pathological changes. CONCLUSIONS Administration of EPO is effective in reversing tissue damage induced by ischemia and/or ischemia/reperfusion in ovaries.

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.

Does telmisartan prevent hepatic fibrosis in rats with alloxan-induced diabetes?

BACKGROUND/AIMS This study evaluated the effect of telmisartan on the livers of diabetic rats and also aimed to determine the hepatic distribution and role of transforming growth factor beta (TGF-beta) in diabetes-related hepatic degeneration while taking into account the possible protective effects of telmisartan. METHODS Fifteen adult male rats were used and divided into three groups: the non-diabetic healthy group, alloxan-induced diabetic control group, and the alloxan-induced diabetic telmisartan group. The non-diabetic healthy group and the diabetic control group were exposed to saline for 30 days, while the group treated with diabetic drugs was orally administered telmisartan for 30 days (10 mg/kg/day). At the end of the experiment, the rats were sacrificed and the livers were dissected and transferred into the fixation solution. The livers were then evaluated using stereological and histopathological methods. RESULTS Our study of the numerical density of hepatocytes shows a significant difference between the diabetic control group and diabetic rats treated with telmisartan. Immunohistochemical staining for TGF-beta in liver sections of the diabetic rats treated with telmisartan showed no immunoreactivity. The diabetic control group was determined to be strongly immunoreactive to TGF-beta. CONCLUSION Results suggest that telmisartan may reduce type-I diabetes mellitus-induced hepatic injury by suppressing activated hepatic stellate cells through concomitant TGF-beta1 down-regulation.

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 (AlCl3) 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) AlCl3 (5 mg/kg/day), (3, 4 and 5) BA (3.25, 36 and 58.5 mg/kg/day), (6, 7 and 8) AlCl3 (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 AlCl3 and AlCl3 + high dose BA (36 and 58.5) treatment groups. However, protective effects on neuron were observed in the AlCl3 + low dose BA (3.25) group when compared other AlCl3 groups. Our stereological and histopathological findings show that low-dose BA, as a proteasome inhibitor, can decrease the adverse effects of AlCl3 on the cerebral cortex.

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 and ovariectomy on rat hippocampus (A biochemical and stereological study)

Oxidative stress is one of the main reasons of both menopause and diabetes. So, it plays crucial role in the pathogeneses of that condition and disease. Therefore, the objective of the present study was to investigate the effects of menopause and diabetes upon the hippocampus using a rat model. Adult female Sprague Dawley rats (n = 24) were allocated randomly as follows; control (C group) ovariectomized (O group), diabetic (D group) and ovariectomy plus diabetic groups (DO group) (n = 6; in each group), respectively. For evaluating the results, tissue biochemistry and stereological analysis were made. Biochemistry results (lipid peroxidase (LPO); catalase (CAT); superoxide dismutase (SOD); total glutatyon (GSH); and myeloperoxidase (MPO) values) in Group C-DO were determined as 12.27, 21.88, 23.08 and 29.90 nmol/gr tissue; 59.3, 70.06, 69.7 and 78.1 mmol/min/mg tissue; 174.2, 156.4, 159.7 and 154.6 mmol/min/mg tissue; 3.63, 3.61, 4.21 and 3.97 nmol/mg tissue; and 5.05, 5.68, 5.58 and 6.19 µmol/min/mg tissue, respectively. Moreover, both menopause and diabetes led to change of lipid profiles. There were significant differences between the control and other groups (Group C and D-DO) (p < 0.01) and among experimental groups (p < 0.01) in terms of neuron number. When the volumes of the hippocampus were compared, there were no significant differences between the all groups (P > 0.05). At this point, we suggested that diabetes could aggravate deleterious effects of ovariectomy.

Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress

Background. Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown. Methods. Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days. Results. We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p < 0.05). Conclusion. Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.