Fehmi Odabasoglu

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.

Beneficial effects of vegetable oils (corn, olive and sunflower oils) and α-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are widely used in the treatment of inflammation, fever and pain. However, NSAIDs cause gastric damage as a major adverse reaction. In this study, the effects of vegetable oils (corn, olive and sunflower oils) and alpha-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin were evaluated in rats. Results showed that indomethacin given with sunflower, corn and olive oils reduced paw edema induced by carrageenan by 79.5%, 74.0% and 60.5%, whereas individual indomethacin and diclofenac reduced paw edema by 56.2% and 50.7%, respectively. Furthermore, it has been found that the vegetable oils possess significant anti-inflammatory effect against paw edema when given alone. These results showed that the vegetable oils have beneficial effects on reduction paw edema induced by carrageenan. Besides, the administration of indomethacin together with the vegetable oils and alpha-tocopherol did not cause a statistically significant gastric damage in rats (P>0.05). However, indomethacin caused statistically significant gastric lesions as compared with untreated rats (P<0.05). Moreover, it was also found that the effects of the vegetable oils and alpha-tocopherol improved the levels of antioxidant defense systems in rat stomach tissues against oxidative damage. These results suggest that indomethacin as well as other NSAIDs do not have any adverse effect on the gastrointestinal tract when they are used together with vegetable oils and vitamin E or as the preparations of the oils.

Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study

Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)‐induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD‐treated CLP group; (ii) 20 mg/kg SLD‐treated CLP group; (iii) CLP group; and (iv) sham‐operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil‐treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham‐operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)‐α level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLP‐induced sepsis via maintenance of the oxidant–anti‐oxidant status and decrease in the level of TNF‐α.

Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats.

One of the common lethal complications of septic shock, a major cause of morbidity and mortality in patients with severe trauma and so on, is acute lung injury. &agr;-Lipoic acid (ALA), with antioxidant properties, is a popular agent. Thus, we investigated the potential protective effects of ALA (200 mg/kg) on sepsis-induced acute lung injury. Rats were exposed to cecal ligation and puncture (CLP) to induce sepsis. Rat groups were designed as (a) sham operated, (b) sham operated + ALA treated, (c) CLP applied, (d) CLP + ALA treated. Sixteen hours after CLP induction, serum samples and lung tissues were obtained for biochemical and histopathological examination. &agr;-Lipoic acid decreased the serum levels of inflammatory cytokines such as TNF-&agr; and IL-6, which increased after CLP. Increased activity of nuclear factor &kgr;B in septic lung tissues was decreased by ALA. &agr;-Lipoic acid improved the decreased antioxidant activity and alleviated the increased oxidant activity, which occurred after CLP application. We can suggest that ALA showed beneficial effects by decreasing nuclear factor &kgr;B activation in lung tissues, resulting in decreased serum levels of TNF-&agr; and IL-6, and also increasing the antioxidant capacity of the lungs.

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.

Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

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.

Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.

An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities.