Biomedical subjects

Berrak C Yeğen

Publications and source records attributed to Berrak C Yeğen.

At least 19 recordsLinked to original sources

PubMed2006

Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, a selective leukotriene CysLT1 receptor antagonist.

Urinary tract infections may induce severe inflammation, transient impairment in renal function and scar formation, ranging in severity from acute symptomatic pyelonephritis to chronic pyelonephritis, which have a potential to lead to renal failure and death. The present study aimed to investigate the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (leukotriene CysLT1), against Escherichia coli-induced oxidative injury and scarring in renal tissue. Wistar rats were injected 0.1 ml of E. coli (ATCC 25922 10(10) cfu/ml) or saline into left renal medullae. Six rats were assigned as the sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or montelukast immediately after surgery and at daily intervals. Twenty-four hours or one week after E. coli injection, rats were decapitated and the kidney samples were taken for histological examination or determination of renal malondialdehyde, glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive oxygen species in renal tissue samples was monitored by using chemiluminescence technique with luminol and lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples. E. coli inoculation caused significant increases in malondialdehyde level, MPO activity, chemiluminescence levels and collagen content, while GSH level was decreased in the renal tissues (p<0.05-0.001). On the other hand, serum TNF-alpha, LDH, blood urea nitrogen and serum creatinine levels were elevated in the pyelonephritic rats as compared to control group. Leukotriene CysLT1 receptor antagonist montelukast reversed all these biochemical indices, as well as histopathological alterations, that were induced by acute pyelonephritis. It seems likely that montelukast protects kidney tissue by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status, and regulating the generation of inflammatory mediators suggesting a future role for leukotriene CysLT1 receptor antagonists in the treatment of pyelonephritis.

Acetates↗

PubMed2006

Propylthiouracil (PTU)-induced hypothyroidism alleviates burn-induced multiple organ injury.

Oxidative stress has an important role in the development of multiorgan failure after major burn. This study was designed to determine the possible protective effect of experimental hypothyroidism in hepatic and gastrointestinal injury induced by thermal trauma. Sprague Dawley rats were administered saline or PTU (10 mgkg(-1) i.p.) for 15 days, and hypothyroidism was confirmed by depressed serum T(3) and T(4) concentrations. Under brief ether anesthesia, shaved dorsum of rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. PTU or saline treatment was repeated at the 12th hour of the burn. Rats were decapitated 24h after injury and tissue samples from liver, stomach and ileum were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also examined microscopically. Tumor necrosis factor (TNF)-alpha and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity, CL levels and collagen content of the studied tissues (p<0.05-0.001). Similarly, serum TNF-alpha and LDH were elevated in the burn group as compared to control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by thermal trauma. Our results suggest that PTU-induced hypothyroidism reduces oxidative damage in the hepatic, gastric and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.

Animals↗

PubMed2006

Ghrelin ameliorates pancreaticobiliary inflammation and associated remote organ injury in rats.

The present study was designed to evaluate whether ghrelin could reduce organ injury and systemic inflammation induced by pancreaticobiliary obstruction. In Sprague-Dawley rats, either the bile duct (BDL) or common pancreaticobiliary duct (PBDL) was ligated or a sham operation was applied. BDL or PBDL rats received either ghrelin (10ng/kg) or saline intraperitoneally immediately before the surgery and once a day until the rats were decapitated at 72h. The pancreas, liver, lung and kidney were removed for the histological analysis, and for the determination of malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase activity (MPO). MDA and MPO levels in all the tissues, which were elevated in PBDL group (p<0.05-0.001), were reversed back to control levels in ghrelin-treated rats. In BDL group, elevations in hepatic MDA and MPO levels (p<0.001) were also abolished by ghrelin treatment. In contrast to saline-treated group with severe pancreatic damage, ghrelin-treated rats demonstrated a moderate pancreatic and hepatic destruction accompanied with reduced pulmonary and renal damages. The results illustrate that ghrelin protects the hepatic and pancreatic tissues, as well as remote organs against oxidative injury, by a neutrophil-dependent mechanism.

Journal Article↗

PubMed2006

Colitis-induced oxidative damage of the colon and skeletal muscle is ameliorated by regular exercise in rats: the anxiolytic role of exercise.

Epidemiological studies have shown that exercise protects the gastrointestinal tract, reducing the risk of diverticulosis, gastrointestinal haemorrhage and inflammatory bowel disease, while many digestive complaints occurring during exercise are attributed to the adverse effects of exercise on the colon. In order to assess the effects of regular exercise on the pathogenesis of colitis, Sprague-Dawley rats of both sexes were either kept sedentary or given exercise on a running wheel (0.4 km h(-1), 30 min for 3 days week(-1)). At the end of 6 weeks, under anaesthesia, either saline or acetic acid (4%, 1 ml) was given intracolonically. Holeboard tests were performed for the evaluation of anxiety at 24 h before and 48 h after induction of colitis. Increased 'freezing time' in the colitis-induced sedentary group, representing increased anxiety, was reduced in the exercised colitis group (P < 0.05). On the third day following the colonic instillation, the rats were decapitated under brief ether anesthesia and the distal 8 cm of the colons were removed. In the sedentary colitis group, macroscopic and microscopic damage scores, malondialdehyde level and myeloperoxidase activity were increased when compared to the control group (P < 0.01-0.001), while exercise prior to colitis reduced all the measurements with respect to sedentary colitis group (P < 0.05-0.001). The results demonstrate that low-intensity, repetitive exercise protects against oxidative colonic injury, and that this appears to involve the anxiolytic effect of exercise, suggesting that exercise may have a therapeutic value in reducing stress-related exacerbation of colitis.

Animals↗

PubMed2006

Beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects.

Methotrexate is an antifolate that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae, where oxidative stress is noticeable. In the present study, the possible protective effect of beta-glucan in methotrexate-induced toxicity was investigated. Following a single dose of methotrexate injection (20 mg/kg), either saline or beta-glucan (50 mg/kg; orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver and kidney were removed to measure tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content, as well as histological examination. Methotrexate caused a significant decrease in GSH levels, while MDA levels, MPO activity and collagen content were increased in all the tissues (P<0.05-0.001). On the other hand, administration of beta-glucan following methotrexate abolished the depletion of GSH and inhibited the increases in MDA, MPO activity and collagen content, while the histological analysis revealed that beta-glucan attenuated the tissue damage. Stimulation index, an indicator of oxidative burst in the neutrophils, was decreased by methotrexate (P<0.001), while beta-glucan abolished this effect. Furthermore, increased leukocyte apoptosis and cell death in methotrexate-treated animals were inhibited by beta-glucan (P<0.05). Thus, the findings of the present study suggest that beta-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis, oxidative tissue injury and thereby the intestinal and hepatorenal side effects of methotrexate treatment.

Animals↗

PubMed2006

Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism.

BACKGROUND: Urinary tract infection (UTI) may cause inflammation of the renal parenchyma and may lead to impairment in renal function and scar formation. Oxidant injury and reactive oxygen species (ROS) have been found responsible in the pathogenesis of UTI. The neurohypophyseal hormone oxytocin (OT) facilitates wound healing and is involved in the modulation of immune and inflammatory processes. We investigated the possible therapeutic effects of OT against Escherichia coli induced pyelonephritis in rats both in the acute and chronic setting. METHODS: Twenty-four Wistar rats were injected 0.1 ml solution containing E. coli ATCC 25922 10(10) colony forming units/ml into left renal medullae. Six rats were designed as sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or OT immediately after surgery and at daily intervals. Half of the pyelonephritic rats were decapitated at the 24th hour of E. coli infection, and the rest were followed for 7 days. Renal function tests (urea, creatinine), systemic inflammation markers [lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-alpha)] and renal tissue malondialdehyde (MDA) as an end product of lipid peroxidation, glutathione (GSH) as an antioxidant parameter and myeloperoxidase (MPO) as an indirect index of neutrophil infiltration were studied. RESULTS: Blood urea, creatinine, and TNF-alpha levels were increased, renal tissue MDA and MPO levels were elevated and GSH levels were decreased in both of the pyelonephritic (acute and chronic) rats. All of these parameters and elevation of LDH at the late phase were all reversed to normal levels by OT treatment. CONCLUSION: OT alleviates oxidant renal injury in pyelonephritic rats by its anti-oxidant actions and by preventing free radical damaging cascades that involves excessive infiltration of neutrophils.

Animals↗

PubMed2006

Montelukast protects against renal ischemia/reperfusion injury in rats.

BACKGROUND: Oxygen free radicals are important components involved in the pathophysiological processes observed during ischemia/reperfusion (I/R). OBJECTIVE: This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on renal I/R injury. METHODS: Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Montelukast (10 mgkg(-1), i.p.) or saline was administered at 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, following decapitation, kidney samples were taken for histological examination or for determination of renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Formation of reactive oxygen species in renal tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples, while leukotriene B4, TNF-alpha, IL-beta, IL-6 and total antioxidant capacity (AOC) were assayed in plasma samples. RESULTS: Ischemia/reperfusion caused a significant decrease in renal GSH and plasma AOC, which was accompanied with significant increases in MDA level, MPO activity, and CL levels of the renal tissue concomitant with increased levels of the pro-inflammatory mediators, LDH activity, creatinine and BUN. On the other hand, montelukast treatment reversed all these biochemical indices as well as histopathological alterations induced by I/R. CONCLUSIONS: CysLT1 receptor antagonist montelukast reversed I/R-induced oxidant responses, improved microscopic damage and renal function. It seems likely that montelukast protects kidney tissue by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status, and regulating the generation of inflammatory mediators.

Acetates↗

PubMed2006

Ginkgo biloba extract protects against ionizing radiation-induced oxidative organ damage in rats.

The present study was designed to determine the possible protective effects of Ginkgo biloba extract (EGb) against oxidative organ damage induced by irradiation (IR). Sprague-Dawley rats were exposed to whole-body IR (800 cGy) after a 15-day pretreatment with either saline or EGb (50 mg/kg/day), intraperitoneally, and treatments were repeated immediately after the IR. Then the rats were decapitated at either 6 h or 72 h after IR, where EGb or saline injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde, glutathione levels, myeloperoxidase activity and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH)-an indicator of tissue damage and TNF-alpha were assayed in serum samples. In the saline-treated irradiation groups, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the tissues (p < 0.01-0.001), which were in parallel with the increases in luminol and lucigenin CL values. In the EGb treated-IR groups, all of these oxidant responses were prevented significantly (p < 0.05-0.01). LDH and TNF-alpha levels, which were increased significantly (p < 0.01-0.001) following IR, were decreased (p < 0.05-0.001) with EGb treatment. In conclusion, the present data demonstrate that EGb, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that EGb may have a potential benefit in enhancing the success of radiotherapy.

Animals↗

PubMed2006

Resveratrol improves ischemia/reperfusion-induced oxidative renal injury in rats.

BACKGROUND: The present study was designed to examine whether resveratrol, a potent antioxidant, protects against renal ischemia-reperfusion (I/R) injury. METHODS: Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Resveratrol (RVT, 30 mg/kg, i.p.) or vehicle was administered twice, at 30 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of levels of renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Renal tissue collagen content as a fibrosis marker was also determined, while serum creatinine and urea concentrations were measured for the evaluation of renal function. Tumor necrosis factor-alpha (TNF-alpha ) and lactate dehydrogenase (LDH) were also assayed in serum samples. RESULTS: Ischemia/reperfusion caused a significant decrease in tissue GSH level, which was accompanied by significant increases in the renal luminol and lucigenin CL values, MDA level, MPO activity and collagen content. Similarly, serum creatinine and BUN levels, as well as LDH and TNF-alpha, were elevated in the I/R group as compared to control group. On the other hand, resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. CONCLUSIONS: Findings of the present study suggest that resveratrol exerts renoprotective effects via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Acridines↗

PubMed2006

Melatonin prevents neutrophil-mediated oxidative injury in Escherichia coli-induced pyelonephritis in rats.

Regarding the mechanisms of renal scarring in pyelonephritis, several hypotheses have been put forward, among which oxidative stress is prominent. The present study investigated the possible protective effect of melatonin treatment against Escherichia coli-induced oxidative injury and scarring in renal tissue. For this purpose, 0.1 mL E. coli (ATCC 25922; 10(10) colony-forming units/mL) or saline was injected directly into the renal parenchyma of Wistar rats. Pyelonephritic rats were treated with either saline or melatonin (10 mg/kg) intraperitoneally. Twenty-four hours or 1 wk after E. Coli injection, rats were decapitated and trunk blood samples were collected for BUN, creatinine, tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) determination. In kidney samples, histological analysis was performed, and malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents were measured. Formation of reactive oxygen species was monitored using a chemiluminescence (CL) technique. Escherichia Coli inoculation caused a significant reduction in renal GSH levels, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the renal tissues (P < 0.05-0.001). Similarly, serum TNF-alpha and, LDH, BUN and creatinine levels were elevated in the pyelonephritic rats when compared with control animals. Melatonin treatment reversed all these biochemical indices, as well as histopathological alterations induced by acute pyelonephritis. The protective effects of melatonin can be ascribed to its ability to inhibit neutrophil infiltration, to balance the oxidant-antioxidant status, and to regulate the generation of inflammatory mediators, suggesting a future role for melatonin in the treatment of acute pyelonephritis.

Animals↗

PubMed2005

Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death.

The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-alpha level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.

Alanine Transaminase↗

PubMed2005

Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast.

BACKGROUND: Sepsis is a generalized inflammatory response, which involves organ systems remote from the locus of the initial infectious insult, involves the release of cytokines and the subsequent formation of reactive oxygen and nitrogen species. OBJECTIVE: The aim of this study was to investigate the possible protective effect of montelukast, a leukotriene receptor blocker, against oxidative damage in the liver and ileum of septic rats. METHODS: Sepsis was induced by cecal ligation and puncture method in female Wistar albino rats. Sepsis and sham operated (control) groups received either saline or montelukast (10 mg/kg, ip) immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, glutathione (GSH) levels--a key antioxidant, myeloperoxidase (MPO) activity--an index of neutrophil infiltration, and collagen contents were determined in the liver and ileum. Formation of reactive oxygen species in liver and ileal tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Both tissues were also analyzed histologically. Serum lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) level were assessed in trunk blood. RESULTS: Sepsis resulted in decreased GSH levels, and increased MDA levels, MPO activity, CL levels and collagen contents in both the liver and the ileum (P < 0.05-P < 0.001) indicating the presence of the oxidative damage. Similarly, serum TNF-alpha and LDH were elevated in the sepsis group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by sepsis. CONCLUSION: Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on sepsis-induced hepatic and intestinal damage and protects against oxidative injury by a neutrophil-dependent mechanism.

Acetates↗

PubMed2005

beta-glucan protects against burn-induced oxidative organ damage in rats.

Thermal injury may lead to systemic inflammatory response, and multiple organ failure. Generation of reactive oxygen radicals and lipid peroxidation play important roles in burn-induced remote organ injury. In the present study, we investigated the putative protective effect of local or systemic beta-glucan treatment on burn-induced remote organ injury. Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce thermal trauma. beta-glucan (3.75 mg/rat locally or 50 mg/kg orally) or saline was administered immediately after the trauma and were repeated twice daily in 48 h groups. Rats were decapitated either 6 or 48 h after burn injury and the skin, lung, liver, ileum and kidney tissues were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase (MPO) activity, while the tumor necrosis factor-alpha (TNF-alpha) levels were measured in serum samples. Skin tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decreases in GSH levels of the liver and intestinal tissues (p<0.01-<0.001), while MDA levels were significantly (p<0.01-p<0.001) increased at post-burn 6 and 48 h. Both local and systemic beta-glucan treatments significantly reversed (p<0.01-p<0.001) the elevations in MDA levels, while reduced GSH levels were reversed back to control levels (p<0.01-p<0.001); and the raised MPO levels were significantly decreased (p<0.05-p<0.001). The results indicate that both systemic and local administration of beta-glucan were effective against burn-induced oxidative tissue damage in the rat. beta-glucans, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, beta-glucans merit consideration as therapeutic agents in the treatment of burn injuries.

Animals↗

PubMed2005

Epidermal growth factor and bombesin act synergistically to support intestinal adaptation in rats with massive small bowel resection.

Intestinal adaptation is the most important event in short bowel syndrome following a massive small bowel resection. Effects of various growth factors and their synergism have been well documented in intestinal adaptation. This study aimed to compare the effect of two different trophic agents, epidermal growth factor (EGF) and bombesin (BBS), on intestinal adaptation following massive intestinal resection. Sprague-Dawley male rats were assigned to one of four groups after a 75% small bowel resection. Either EGF (90 microg/kg), BBS (10 microg/kg), EGF+BBS, or bovine serum albumin (BSA) were injected subcutaneously three times a day. The animals were killed 10 days after the operation. Weight loss and morphologic parameters such as mucosal thickness, villus height, crypt depth, villus-to-crypt ratio, and muscularis propria height were measured. In the EGF+BBS group, mucosal thickness was found to be significantly increased compared with the other study groups (p<0.05). Similarly, villus height was significantly increased only in the EGF+BBS group (p<0.05). In the BBS group, both villus height and mucosal thickness showed a slight increase, but the values were not statistically significant compared with the vehicle-treated group. There were no significant differences in any of the remaining parameters between the groups. The results of this study indicate that the gut hormones EGF and BBS act synergistically in facilitating the adaptive response of the remnant ileum to massive intestinal resection.

Adaptation, Physiological↗

PubMed2005

Estrogen protects the liver and intestines against sepsis-induced injury in rats.

BACKGROUND AND AIM: Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. MATERIALS AND METHODS: Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. RESULTS: In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P < 0.01 to P < 0.001), suggesting oxidative organ damage, which was also verified histologically. In the estradiol-treated sepsis group, all of these oxidant responses were reversed significantly (P < 0.05 to P < 0.01). Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. CONCLUSION: The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

Animals↗

PubMed2005

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.

Animals↗

PubMed2005

Melatonin protects against oxidative organ injury in a rat model of sepsis.

PURPOSE: Based on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against sepsis-induced oxidative organ damage in rats. METHODS: Sepsis was induced by cecal ligation and puncture (CLP) in Wistar albino rats. Animals subjected to CLP and sham-operated control rats were given saline or melatonin 10 mg/kg intraperitoneally 30 min before and 6 h after the operation. The rats were killed 16 h after the operation and the biochemical changes were investigated in the liver, kidney, heart, lung, diaphragm, and brain tissues by examining malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. We also examined the tissues microscopically. RESULTS: Sepsis resulted in a significant decrease in GSH levels and a significant increase in MDA levels and MPO activity (P < 0.05-P < 0.001) showing oxidative damage, which was confirmed by histological examination. Melatonin clearly reversed these oxidant responses and the microscopic damage, demonstrating its protective effects against sepsis-induced oxidative organ injury. CONCLUSION: The increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage. Melatonin, by its free radical scavenging and antioxidant properties, ameliorated oxidative organ injury. Thus, supplementing antiseptic shock treatment with melatonin may be beneficial in the clinical setting.

Analysis of Variance↗

PubMed2005

Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs.

Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.

Acetates↗