Barış Çakır

The anti-inflammatory effect of leptin on experimental colitis: involvement of endogenous glucocorticoids.

The present study was designed to compare the effect of leptin on acute colonic inflammation with that of acute stress exposure, which acts via the hypothalamic-pituitary-adrenal (HPA) axis. Sprague-Dawley rats of both sexes were administered intrarectally with acetic acid. Either leptin (10 microg/kg; i.p.) or saline was injected immediately before and 6 h after the induction of colitis. A group of rats was exposed to water avoidance stress (WAS) for 30 min at the 6th h of colitis induction. RU-486 (2 mg/kg; i.p.), a glucocorticoid receptor antagonist, was injected intraperitoneally, at 12 and 1 h before the initial leptin injection, and at 1 h before the second leptin injection or exposure to WAS. Rats were decapitated at 24 h and the distal 8 cm of the colon were removed for macroscopic and microscopic scoring, determination of tissue wet weight index (WI) and tissue myeloperoxidase activity (MPO). Acetic acid-induced colitis significantly increased macroscopic and microscopic damage scores, WI and MPO, compared to control group. Exposure to acute WAS or treatment with leptin reduced the elevations in damage scores, WI and MPO induced by colitis, but no additive inhibitory effect was observed when WAS and leptin were applied together. RU-486 treatment reversed the inhibitory effects of leptin or WAS on colonic inflammation. Our results demonstrate that exogenous leptin mimics the effects of HPA axis activation on colitis-induced inflammatory process. The results also suggest that the anti-inflammatory effect of leptin involves a tissue neutrophil-dependent mechanism and is dependent on the release of glucocorticoids.

Anti-inflammatory effects of leptin and cholecystokinin on acetic acid-induced colitis in rats: role of capsaicin-sensitive vagal afferent fibers

Leptin and cholecystokinin (CCK) have a synergistic interaction in the suppression of food intake, and afford similar gastroprotective activity. The present study was designed to investigate the putative protective effects of CCK and leptin on acute colonic inflammation. Leptin or CCK-8s was injected to rats intraperitoneally immediately before and 6 h after the induction of colitis with acetic acid. CCK-A receptor antagonist (L-364,718) or CCK-B receptor antagonist (L-365,260) was injected intraperitoneally 15 min before leptin or CCK treatments. In a group of rats, vagal afferent fibers were denervated by topical application of capsaicin on the cervical vagi. Rats were decapitated at 24 h, and the distal 8 cm of the colon were removed for macroscopic scoring, determination of tissue wet weight index (WWI), histologic assessment and tissue myeloperoxidase (MPO) activity. All inflammation parameters were increased by acetic acid-induced colitis compared to control group. Leptin or CCK-8s treatment reduced these parameters in a similar manner, while co-administration of leptin and CCK was found to be more effective in reducing the macroscopic score and WWI. CCK-8s-induced reduction in the score and WWI was prevented by CCK-A, but not by CCK-B receptor antagonist, whereas neither antagonist altered the inhibitory effect of leptin on colitis-induced injury. On the other hand, perivagal capsaicin prevented the protective effects of both CCK-8s and leptin on colitis. Our results indicate that leptin and CCK have anti-inflammatory effects on acetic acid-induced colitis in rats, which appear to be mediated by capsaicin-sensitive vagal afferent fibers involving the reduction in colonic neutrophil infiltration.

Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats

The present study was designed to determine whether exogenous leptin reduces remote organ injury in the rats with thermal burn trauma. Leptin (10 microg/kg) or saline was administered intraperitoneally after burn injury, and the rats were decapitated at either 6 or 24 h. Plasma samples of 24-h burn group were assayed for the determination of monocyte and neutrophil apoptosis. Thermal injury increased tissue-associated myeloperoxidase (MPO) activity and microscopic damage scores in the lung, liver, stomach, colon and kidney of both 6- and 24-h burn groups. In the 6-h burn group, leptin reduced microscopic damage score in the liver and kidney only, while damage scores in the 24-h burn group were reduced in all the tissues except the lung. Also, in both burn groups, leptin reduced elevated MPO activity in all tissues except the lung. The percentage of mononuclear cells was significantly reduced at the 24 h of burn injury, while the granulocyte percentage was increased. Leptin treatment, however, had no significant effect on burn-induced reversal of white blood cell ratios. On the other hand, burn-induced increase in the death of mononuclear cells and granulocytes was significantly reduced in leptin-treated rats. The results of the present study suggest that leptin may provide a therapeutic benefit in diminishing burn-induced inflammation and associated multiple organ failure.

Stress-induced multiple organ damage in rats is ameliorated by the antioxidant and anxiolytic effects of regular exercise

Our aim was to investigate the effects of moderate load, regular swimming exercise on stress‐induced anxiety, and associated oxidative organ injury. Male Sprague‐Dawley rats (n = 48) were either kept sedentary or submitted to swimming exercise for 8 weeks. Rats were then divided as non‐stressed, acute stress, and chronic stress groups. After acute or chronic stress (electric foot shocks) applications, rats were placed on a holeboard and the exploratory behavior was recorded to assess the anxiety. Rats were decapitated after the stress application. Acute and chronic stress induction led to increased serum cortisol levels as compared to non‐stressed groups. Plasma aspartate aminotransferase levels that were elevated in sedentary rats with both stress exposures were lower in trained rats. Malondialdehyde levels and myeloperoxidase activity were increased in the cardiac muscle, liver, stomach, and brain of the stressed rats with a concomitant reduction in the glutathione levels, while stress‐induced changes in malondialdehyde, myeloperoxidase, and glutathione levels were reversed in the trained animals. Exercise, which led to increased malondialdehyde and reduced glutathione levels in the skeletal muscle of the non‐stressed rats, also protected against stress‐induced oxidative damage. Regular exercise with its anxiolytic and antioxidant effects ameliorates stress‐induced oxidative organ damage by a neutrophil‐dependent mechanism. Copyright

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

The impact of sex dimorphism on chronic renal failure (CRF)-induced oxidative multiorgan damage and the effects of estradiol (E2) loss and E2 supplementation on the progress of CRF were studied. Sprague-Dawley rats underwent 5/6 nephrectomy (CRF), and a group of female rats had bilateral ovariectomy (OVX), while the sham-operated rats had no nephrectomy or OVX. Rats received either estradiol propionate (50 μg/kg/day) or vehicle for six weeks. Serum BUN levels were elevated in both male and female CRF groups treated with vehicle, while creatinine level was not significantly changed in the female CRF group. CRF-induced elevation in serum TNF-α of male rats was abolished when the animals were treated with E2, while OVX exaggerated TNF-α response. In OVX and male rats with CRF, E2 treatment reversed the malondialdehyde elevations in all the studied tissues (kidney, heart, lung, ileum, brain, liver, and gastrocnemius muscle), while depletion of glutathione in these tissues was prevented by E2 treatment. Similarly, increased levels of myeloperoxidase activity, lucigenin chemiluminescence, and collagen in most of the tissues were reversed by E2 treatment. The findings show that the extent of tissue injuries was relatively less in females, while ovariectomy exacerbated all the indices of oxidative injury. Moreover, the administration of E2, with its potent anti-oxidant and anti-inflammatory effects, markedly improved CRF-induced systemic inflammatory outcomes in both male and female rats by depressing tissue neutrophil infiltration and modulating the release of inflammatory cytokines.

Protective role of cyclooxygenase (COX) inhibitors in burn-induced intestinal and liver damage

The aim of this study was to investigate the role of cyclooxygenase (COX) inhibition in intestinal motility and in the extent of tissue injury of the small intestine and liver with the use of various COX inhibitors. Wistar albino rats were exposed to 90 degrees C water bath for 10s. The intestinal transit index decreased compared to control group and treatment with nimesulide (NIM; 10mg/kg, subcutaneously) or piroxicam (Pir; 5mg/kg, orogastrically) reversed this effect significantly. The intestinal and liver glutathione levels showed a significant decrease in the burn group compared to sham (P<0.001 and P<0.05, respectively). Decrease in intestinal glutathione level was reversed by NIM or Pir treatment (P<0.01 and P<0.01, respectively), whereas all drugs tested were effective in reversing low liver glutathione level. The MPO activity in intestinal segments were significantly high in burned animals compared to sham. All test drugs reversed this effect but ketorolac (Ket; 3mg/kg, orogastrically) was the most effective one. The liver samples characterized by sinusoidal dilatation and pericentral atrophy in burn group were protected by treatment with Ket or Pir (P<0.05). Plasma ALT and AST activities were markedly high in this burn group compared to sham (P<0.0001 and P<0.001, respectively). None of the agents reversed these high enzyme activities. These data suggest that not only COX-2 but also COX-1 inhibition is required for protection against inflammatory changes in liver and small intestine following burn injury.

Rating Of Perceived Exertion In Cycle Ergometer: Effect Of Maximal Capacity Differences

The purpose of this study was to evaluate cardiopulmonary responses of individuals with different fitness levels according to predetermined rating of perceived exertion (RPE) scores and to investigate the correspondence between the heart rate reserve percentage (HRR%) and the RPE scale by using fit and unfit subjects. Materials and methods: RPE scores of sedentary volunteers were recorded at different HRR% levels during graded exercise tests on a cycle ergometer. Following the tests, subjects were divided into 2 groups, high metabolic equivalent [(MET) MET >= 10; n = 9] and low MET (MET < 10; n = 11), according to maximal O2 uptakes (VO2max). Participants performed the steady-state exercise test at the 13th-14th level of their perceived exertion 48 h after the first test. Variance and regression analyses were performed. Results: For all HRR% values, RPE levels were not different between groups. During the graded exercise test, perceived exertion was significantly higher in the low MET group than in the high MET group. Predetermined RPE score results were significantly greater in the low MET group with relative O2 consumption as compared to the high MET group (P < 0.05-0.001). Conclusion: In individuals with different VO2max levels, exercise intensity can be prescribed using HRR% or RPE scale methods while adjusting for individual differences in oxygen consumption.