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Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linked with bariatric surgery outcomes, gastric production of these peptides was not elucidated before. The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass. Physiology Research Lab at the University. Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 β, ER-α agonist, ER-β agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemical measurements, while histopathologic examination was performed in gastric and femur samples. In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrin-expressing cells, ameliorated gastric injury, and improved bone loss. SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications. • Sleeve gastrectomy (SG) reduced gastric levels of gastrin and leptin. • Gastric GLP-1 content is elevated with ovariectomy, but reduced by SG. • SG elevated depleted serum estradiol level, but resulted in gastric mucosal injury. • Estrogen receptor agonists ameliorated gastric injury and improved bone loss. [ABSTRACT FROM AUTHOR]

This study used an experimental model mimicking early postoperative enteral feeding after the transfer of free jejunal flap and tested the hypothesis that jejunal infusion with dextrose or saline is associated with improved tissue perfusion and/or less mucosal damage after ischemia/reperfusion (IR) injury. Thirty-five male Sprague Dawley rats were randomly divided into five groups: sham group (no IR and no intraluminal infusion); IR control group (IR but not intraluminal infusion); IR plus intraluminal 0.9% NaCl infusion or 5% dextrose or 10% dextrose infusion groups. A jejunal segment of each rat was isolated. The animals had jejunal ischemia for 40 min, reperfusion, and intestinal infusion on the basis of their allocation. Jejunal tissue perfusion was measured with laser Doppler flowmetry at one hour and two hours after reperfusion, after which the animals were sacrificed and tissue samples were obtained for the scoring of histological damage at superficial and cryptic epithelium, villus structure, and inflammatory cell infiltration and tissue nitric oxide (NO), interleukin (IL)-1, IL-6, and matrix metalloproteinase-1 (MMP) level measurements. At 1 h of reperfusion, IR plus 5% dextrose and 10% dextrose groups both had significantly higher perfusion rates than the IR control group (384.8 ± 26.7 and 462.4 ± 44.7 versus 270.3 ± 34.2 PU, respectively, p < 0.05 for both). These differences were maintained at 2 h of reperfusion (p < 0.05 for both). Saline infusion, however, resulted in improved tissue perfusion only at the early phase of reperfusion. Intraluminal infusion with dextrose solution, either 5% or 10%, was associated with higher tissue NO, IL-1, and IL-6 levels than that in the sham group (p < 0.05 for all). In addition, intraluminal infusion of any fluid resulted in less severe histological damage (8.1 ± 0.9 versus 5.8 ± 1.0, 5.4 ± 0.9, and 5.2 ± 1.9, for IR plus saline, 5% dextrose and 10% dextrose groups, respectively, p < 0.05 for all). Intraluminal infusion of fluids, particularly dextrose solutions, may be protective against IR injury as demonstrated by improved tissue perfusion and less histological damage. In addition, increases in tissue NO, IL-1, and IL-6 levels in association with dextrose infusion may be explained by the activation of pro-inflammatory and anti-inflammatory protective pathways. These support early enteral feeding after free jejunum flap transfers; however, further studies are warranted. [ABSTRACT FROM AUTHOR]

Highlights • Moderate swimming exercise (EXC) ameliorated high fat diet induced cardiac and aortic tissue damages. • Moderate EXC modulates oxidative stress and NO activity, in both cardiac and aortic tissues. • EXC may protect obesity-induced cardiac and aortic damage by regulating the balance of oxidants/antioxidants and NO metabolism. Abstract We investigated the protective effects of swimming exercise on high-fat diet-induced heart and aorta damage by evaluating oxidative stress and the endothelial nitric oxide (NO) system. Sprague Dawley rats were fed either standard chow (STD, 6% fat) or high-fat diet (HFD; 45% fat) for 18 weeks, with half of the animals trained by daily swimming sessions (EXC; 1 h per day for 5 days/week) for the last 6 weeks of the experimental period and half kept sedentary (SED). Heart and aorta tissues were prepared for routine light and electron microscopy evaluation. Endothelial NOS (eNOS) and inducible NOS (iNOS) distribution in the tissue samples were examined by immunohistochemistry. Biochemical examinations, including blood serum lipid profiles, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and tissue NO levels were measured. Deteriorated heart and aorta morphology, increased MDA levels and iNOS-immunoreactivity (iNOS-ir), as well as decreased GSH, NO, SOD, and eNOS-ir parameters were observed in the HFD + SED group. These morphological and biochemical parameters were ameliorated in the HFD + EXC group. Our study revealed that obesity-induced iNOS activation and increased oxidative stress in cardiac and aorta tissues. Exercise protected the obesity-induced cardiac and aortic tissue damage by modulating oxidant/antioxidant balance via involvement of the NO system. [ABSTRACT FROM AUTHOR]

This study evaluated ulceroprotective and antioxidant effect of 1,25 dihydroxyvitamin D3 against gastric damage in rats. Rats were treated intraperitoneally with either 1,25 dihydroxyvitamin D3 (0.25 μg/kg) or saline for 14 days. On day-15, the non-selective cyclooxygenase inhibitor indomethacin (10 mg/kg; subcutaneously), the inhibitor of sulfhydryl groups N-ethylmaleimide (10 mg/kg; intraperitoneally) or ATP-sensitive K+ channel blocker glibenclamide (10 mg/kg; orally) was given prior to 1,25 dihydroxyvitamin D3. Animals were euthanized at 60 min post ulcerogenic challenge (0.3 M HCl and 60% ethanol (0.2 mL; orally). Stomach and blood were collected for biochemical and histological evaluations. HCl/Ethanol group revealed severely damaged mucous and glandular epithelium with diffuse hemorrhage and inflammatory cell infiltration (microscopic score: 10.67 ± 0.67 and ulcer index: 33.13 ± 5.09). 1,25 dihydroxyvitamin D3 decreased the extent of damage (microscopic score: 6.80 ± 0.02 and ulcer index: 19.00 ± 4.34; p < 0.05), and the elevations in gastric malondialdehyde level (p < 0.001), myeloperoxidase activity (p < 0.001), nuclear factor-κB expression (p < 0.05), and apoptotic index (p < 0.05) following HCl/Ethanol challenge. Decreased gastric glutathione following HCl/Ethanol administration was restored by 1,25 dihydroxyvitamin D3 (p < 0.01). These findings demonstrated protection of the gastric mucosa against HCl/Ethanol-induced injury by 1,25 dihydroxyvitamin D3 via attenuation of inflammatory reaction, oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Objective This study was designed to examine the possible protective effect of apocynin, a NADPH oxidase inhibitor, against torsion/detorsion (T/D) induced ischemia/reperfusion (I/R) injury in testis. Methods Male Wistar albino rats were divided into sham-operated control, and either vehicle, apocynin 20 mg/kg- or apocynin 50 mg/kg-treated T/D groups. In order to induce I/R injury, left testis was rotated 720° clockwise for 4 hours (torsion) and then allowed reperfusion (detorsion) for 4 hours. Left orchiectomy was done for the measurement of tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol, lucigenin, nitric oxide (NO) and peroxynitrite chemiluminescences (CL). Testicular morphology was examined by light microscopy. Results I/R caused significant increases in tissue luminol, lucigenin, nitric oxide and peroxynitrite CL demonstrating increased reactive oxygen and nitrogen metabolites. As a result of increased oxidative stress tissue MPO activity, MDA levels were increased and antioxidant GSH was decreased. On the other hand, apocynin treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. According to data, although lower dose of apocynin tended to reverse the biochemical parameters, high dose of apocynin provides better protection since values were closer to the control levels. Conclusion Findings of the present study suggest that NADPH oxidase inhibitor apocynin by inhibiting free radical generation and increasing antioxidant defense exerts protective effects on testicular tissues against I/R. The protection with apocynin was more pronounced with high dose. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of platelet-rich fibrin (PRF) on the early bone healing process with bone scintigraphy based on technetium-99m methylene diphosphonate uptake in third molar extraction sockets. Patients and Methods: Fourteen patients with bilaterally soft tissue impacted third mandibular molars were included in the study. The right and left impacted third molars were surgically extracted in the same session. PRF was randomly administered into one of the extraction sockets, whereas the contralateral sockets were left without treatment. Four weeks after surgery, scintigrams were obtained to evaluate scintigraphic differences between PRF-treated and non–PRF-treated sockets. After completion of the clinical study, PRF samples were evaluated by light and scanning electron microscopy. Results: The average increase in technetium-99m methylene diphosphonate uptake as an indication of enhanced bone healing did not differ significantly between PRF-treated and non–PRF-treated sockets 4 weeks postoperatively (P > .05). Abundant fibrin and inflammatory cells were observed by light microscopic examination of PRF samples. Scanning electron microscopic analysis of PRF revealed the existence of platelet aggregates in a fibrin network and crystalline particles on the outer surface of PRF. Conclusions: PRF might not lead to enhanced bone healing in soft tissue impacted mandibular third molar extraction sockets 4 weeks after surgery. PRF exhibits the potential characteristics of an autologous fibrin matrix. However, whether the presence of crystal-like particles on the outer surface of PRF alters bone healing should be investigated further. [Copyright &y& Elsevier]

Abstract: We investigated the role of montelukast (ML), a cysteinyl leukotriene-1 receptor antagonist, on the water avoidance stress (WAS)-induced degeneration of the rat gastric, ileal and colonic mucosa. One group of Wistar albino rats were exposed to chronic WAS (WAS group) 2h daily for 5 days. Another group was administered ML (10mg/kg; i.p.; WAS+ML group) following every WAS exposure for 5 days. Control rats were injected with the vehicle solution only. The stomach, ileum and colon were dissected and investigated for histopathological changes with a light microscope as well as for topographical changes with a scanning electron microscope. The levels of malondialdehyde (MDA, a biomarker of oxidative damage) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. In the WAS group, the stomach epithelium showed ulceration in some areas, dilatations of the gastric glands, degeneration of gastric glandular cells, and prominent congestion of the capillaries. In a similar fashion, degenerated epithelium and severe vascular congestions were observed in the ileum and colon. In all the tissues dense inflammatory cell infiltration and mast cell degranulation in mucosa were observed. The levels of MDA were significantly increased whereas those of GSH were significantly decreased in all test tissues in the WAS group compared to the control group. The morphology of gastric, ileal and colonic mucosa in WAS+ML group showed a significant amelioration showing a reduction in inflammatory cell infiltration and mast cell degranulation. Increased MDA and decreased GSH levels in the WAS group were also ameliorated with ML treatment. Based on the results, ML supplement seems attenuated inflammatory effects of WAS induction in gastrointestinal mucosa. [Copyright &y& Elsevier]

Abstract: Statins have anti-inflammatory effects that are not directly related to their cholesterol-lowering activity. This study aimed to investigate the effect of simvastatin on the extent of tissue damage in cisplatin-induced nephrotoxicity and hepatotoxicity. The rats received a single intravenous injection of 2.5mgkg−1 cisplatin. Other groups received either simvastatin (1mgkg−1) or the vehicle (ethanol:saline) intraperitoneally for 10 days beginning 5 days prior to cisplatin injection. All animals were decapitated 5 days after cisplatin administration. Trunk blood was collected and analyzed for blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), albumin, and total bilirubin levels. The urine samples were used for the calculation of creatinine clearance levels. The kidney and liver samples were stored for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content or were processed for histopathological examinations. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence method. Simvastation reduced the extent of both kidney and liver damage and preserved both kidney and liver functions (p <0.01–0.001). Increase in liver MDA level with a concomitant reduction in GSH in the cisplatin group was attenuated by simvastatin treatment (p <0.05–0.01). Increase in tissue collagen content and chemiluminescence levels in the kidney and liver samples of the cisplatin group was also reversed by simvastatin (p <0.001). In conclusion, simvastatin is beneficial in cisplatin-induced kidney and liver dysfunction and organ damage in rats via prevention of lipid peroxidation and tissue fibrosis, preservation of antioxidant glutathione, and suppression of neutrophil infiltration. [Copyright &y& Elsevier]

Abstract: Substance P is a neuropeptide involved in inflammation, immune regulation and stress response. Stress may induce bladder damage by stimulating inflammatory response such as mast cell activation. We here examined the role substance P during stress-induced mast cell degranulation and urothelial injury in rat bladder. Adult Sprague-Dawley rats (200–270 g) were either exposed to cold-immobilization stress or substance P (SP) intracerebroventricularly. Different doses of substance P receptor (NK1R) antagonist CP 99994 were administered peripherally or centrally before the stress exposure. From each group, samples of the bladder were examined with light and electron microscope. Stress- and SP-injected centrally, increased the number of both granulated and degranulated mast cells. Ultrastructurally, urothelial degeneration with vacuolization in the cytoplasm and dilated intercellular spaces were seen. Both central and peripheral injection of CP 99994 prevented stress-induced urothelial degeneration as well as stress-induced mast cell degranulation. In conclusion, centrally and peripherally released substance P is involved in stress-induced bladder damage. Inhibition of NK1R prevents stress-induced pathological changes of urinary bladder and NK1R antagonist can be considered for the treatment of inflammatory bladder diseases. [Copyright &y& Elsevier]

Abstract: 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 (10mg/kg, ip) immediately after the operation and at 12h. 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- (TNF-α) 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 () indicating the presence of the oxidative damage. Similarly, serum TNF-α 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. [Copyright &y& Elsevier]

Abstract: The present study was aimed to investigate the effect of ACE inhibition on trinitrobenzene sulphonic acid (TNBS)-induced colonic inflammation in rats by using captopril and lisinopril. In treatment groups, the rats were treated with ACE inhibitors, captopril or lisinopril (0.1 and 1 mg/kg/day; intraperitoneally). The drugs were given 5 min after induction of colitis and the treatment was continued for 3 days. Three days after the induction of colitis, all rats were decapitated. The distal colon was weighed and the mucosal lesions were scored at both macroscopical at microscopic levels. Malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were assessed in tissue samples. Formation of reactive oxygen species in colonic samples was monitored by using chemiluminescence technique. Serum TNF-αlevel was assessed in trunk blood. Captopril treatment was found to be beneficial in all parameters, except colonic glutathione content. On the other hand, although stimulation of lipid peroxidation and increase in serum TNF-α level were successfully prevented by lisinopril, the morphology of the lesions remained unchanged. In conclusion, sulphydryl and non-sulphydryl ACE inhibitors, captopril and lisinopril do not seem to be similarly effective in TNBS-induced colitis model at least at the doses tested in our study. [Copyright &y& Elsevier]

Summary: Nontraumatic psychological water avoidance stress has been shown to induce mucosal degeneration, inflammatory cell infiltration and mast cell degranulation in stomach, ileum, colon and urinary bladder. Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and seem to be related with infiltration and activation of mast cells releasing vasoactive and proinflammatory mediators. Melatonin is a free radical scavenger and has cytoprotective effects in inflammatory conditions. The aim of the present study was to investigate the effects of melatonin on water avoidance stress (WAS)-induced degranulation of mast cells in the dermis. Wistar rats were exposed to acute WAS (aWAS group) or chronic WAS (cWAS group). Before exposing to acute WAS, one group of animals was treated with 10mg/kg melatonin (aWAS+mel group). In the cWAS+mel group, treatment with melatonin lasted for 5 days. Dermal mast cells were stained with toluidine blue and investigated using light microscopy. Numbers of mast cells were increased in both aWAS and cWAS groups, but numbers of degranulated mast cells were increased significantly only in the cWAS group when compared to the control group. Numbers of mature granulated and degranulated mast cells were decreased in the cWAS+mel group when compared to the cWAS group. In conclusion, chronic melatonin treatment reduced WAS-induced infiltration and activation of mast cells in dermis and may provide a useful therapeutic option in stress-induced skin disorders. [Copyright &y& Elsevier]

Small bowel is one of the organs that can in principle be transplanted. Optimum preservation of the organ is essential for the success of transplantation. The aim of the present study is the investigation of time-related morphological changes of rat small bowel during preservation in hypothermic Euro-Collins (EC) and Ringer''s lactate (RL) solution using light microscopy and transmission electron microscopy to evaluate the integrity of intercellular complexes of mucosal epithelium, one of the tissues of the intestine that is most susceptible to ischemia. Small bowels were perfused with either EC, RL solution or physiological saline solution and were placed in the different preservation solutions at 4°C for 0, 3, 6 and 12 h. The results of our study suggest that both preservation solutions are suitable for short-term preservation of the small bowel although RL solution is more effective than EC solution. However, we conclude that further improvement of preservation solutions and/or techniques are needed to perform long-term preservation. [Copyright &y& Elsevier]

Cardiovascular diseases (CVDs), with highest mortality and morbidity rates, are the major cause of death in the world. Due to the limited information on heart tissue changes, mediated by hypercholesterolemia, we planned to investigate molecular mechanisms of endoplasmic reticulum (ER) stress and related cell death in high cholesterol fed rabbit model and possible beneficial effects of α-tocopherol. Molecular changes in rabbit heart tissue and cultured cardiomyocytes (H9c2 cells) were measured by western blotting, qRT-PCR, immunflouresence and flow cytometry experiments. Histological modifications were assessed by light and electron microscopes, while degradation of mitochondria was quantified through confocal microscope. Feeding rabbits 2% cholesterol diet for 8 weeks and treatment of cultured cardiomyocytes with 10 μg/mL cholesterol for 3 h induced excessive autophagic activity via IRE1/JNK pathway. While no change in ER-associated degradation (ERAD) and apoptotic cell death were determined, electron and confocal microscopy analyses in cholesterol supplemented rabbits revealed significant parameters of autophagic cell death, including cytoplasmic autophagosomes, autolysosomes and organelle loss in juxtanuclear area as well as mitochondria engulfment by autophagosome. Either inhibition of ER stress or JNK in cultured cardiomyocytes or α-tocopherol supplementation in rabbits could counteract the effects of cholesterol. Our findings underline the essential role of hypercholesterolemia in stimulating IRE1/JNK branch of ER stress response which then leads to autophagic cell death in heart tissue. Results also showed α-tocopherol as a promising regulator of autophagic cell death in cardiomyocytes. • High cholesterol induces endoplasmic reticulum stress • IRE1-JNK branch of endoplasmic reticulum stress regulates autophagic cell death • α-Tocopherol alleviates cardiomyocyte loss by affecting autophagic activity [ABSTRACT FROM AUTHOR]

Abstract: Smoking causes subfertility due to deterioration of spermatozoa including decreased concentration and abnormal morphology. Although evidence on the deleterious effects of smoking on spermatozoa parameters is well known, its interference with cryopreservation is not clear. This study aimed to investigate the effects of cryopreservation on sperm parameters and DNA fragmentation in non-smokers and smokers. Semen samples were obtained from 40 normospermic male volunteers of whom 20 were non-smokers and 20 smokers. Samples were analyzed in terms of motility, concentration, morphology, and DNA fragmentation before freezing and 1 and 3 months after freezing and thawing. Ultrastructural alterations were investigated by transmission electron microscopy. Sperm morphology seemed to be more affected after cryopreservation in samples obtained from smokers. Ultrastructural examination showed alterations in the integrity of the membranes and increased subacrosomal swelling. Before freezing, the increase in DNA fragmentation rate in smokers was not statistically significant compared to that of non-smokers. However, after thawing, the DNA fragmentation rates were significantly high in both non-smokers and smokers compared to their respective rates before freezing. The extent of the increase in DNA fragmentation rate was significantly higher in smokers after thawing compared to that of non-smokers. In conclusion, cryopreservation causes alterations in membrane integrity and increases DNA fragmentation, thus triggering relatively negative effects on the sperm samples of smokers compared to that of non-smokers. [Copyright &y& Elsevier]

Abstract: Aims: To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant–antioxidant status and apoptosis in rats with colitis. Main methods: Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30mg/ml; 0.8ml) given intrarectally to Sprague–Dawley rats. Sildenafil (25mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-10 assays. Key findings: The macroscopic lesion score of the colitis group was reduced by SIL (p<0.01) and this effect was abolished by l-NAME (p<0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p<0.01 and p<0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p<0.001). Sildenafil also reduced the elevated MPO of the colitis group (p<0.001) and this effect was reversed by L-NAME (p<0.01). Increase in lucigenin CL and serum TNF-α levels in the colitis group were also prevented by SIL (p<0.001 and p<0.01, respectively). Significance: Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant–antioxidant status, prevention of apoptosis, superoxide production and cytokine release. [Copyright &y& Elsevier]

Abstract: Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia–reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes (∼70%) for 30min of ischemia followed by 1h reperfusion in female Sprague–Dawley rats under anesthesia. I/R group (n =8) was administered intraperitoneally either OT (500μg/kg) or saline at 24 and 12h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-α) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-α levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-α levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration. [Copyright &y& Elsevier]

Summary: The present study was designed to investigate dynein arm and microtubule defects quantitatively in patients with respiratory disease and to establish the clinical relevance of dynein arm deficiency and microtubule abnormalities. Thirty-four patients with recurrent upper and/or lower respiratory infections were included in the study. Nasal mucosal brushings were fixed in glutaraldehyde and routine electron microscopic procedures were carried out. At least 20 cross-sectioned cilia were examined from each subject. Dynein arm and microtubular abnormalities were quantified and a statistical analysis was performed. Twenty-nine percent of the patients showed dynein arm deficiency and a further 21% had possible deficiency (PD). Microtubule defects in patients with dynein arm deficiency and PD were found to be significantly increased compared to the patients with no dynein arm deficiency. The most prominent defect in the dynein arm deficiency group was a translocation of central and/or peripheral microtubules. The high percentage of translocation defect in this group of patients suggests that these defects are primary, rather than secondary to infection. [Copyright &y& Elsevier]

Abstract: Sepsis leads to various organ damage and dysfunction. One of the underlying mechanisms is thought to be the oxidative damage due to the generation of free radicals. In this study, we investigated the putative protective role of β-glucan against sepsis-induced oxidative organ damage. Sepsis was induced by caecal ligation and puncture (CLP) in Wistar albino rats. Sham operated (control) and sepsis groups received saline or β-glucan (50 mg/kg, po) once daily for 10 days and 30 min prior to and 6 h after the CLP. Sixteen hours after the surgery, rats were decapitated and the biochemical changes were determined in the brain, diaphragm, kidney, heart, liver and lung tissues using malondialdehyde (MDA) content – an index of lipid peroxidation – glutathione (GSH) levels – a key antioxidant – and myeloperoxidase (MPO) activity – an index of neutrophil infiltration. Serum TNF-α levels were assessed by RIA method. Tissues were also examined under light microscope to evaluate the degree of sepsis-induced damage. The results demonstrate that sepsis significantly decreased GSH levels and increased the MDA levels and MPO activity (p &#60;0.05–p &#60;0.001) causing oxidative damage. Elevated plasma TNF-α levels in septic rats significantly reduced to control levels in β-glucan treated rats. Since β-glucan administration reversed these oxidant responses, it seems likely that β-glucan protects against sepsis-induced oxidative organ injury. [Copyright &y& Elsevier]

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 μg/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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

: ObjectivesTo evaluate the morphologic changes in rat urothelium induced by indomethacin. Nonsteroidal anti-inflammatory drug-induced cystitis is a poorly recognized and under-reported condition. In addition to tiaprofenic acid, indomethacin has been reported to be associated with this condition.: MethodsThree groups were established: a control group (n = 10), a high-dose group (n = 10), treated with one intraperitoneal injection of indomethacin 20 mg/kg, and a therapeutic dose group (n = 10) in which oral indomethacin was administered 3.25 mg/kg body weight daily for 3 weeks. The animals were then killed and the bladders removed for light and electron microscopic studies.: ResultsThe light microscopic findings showed some focal epithelial degeneration that was more prominent in the high-dose group. When compared with the control group, both indomethacin groups revealed statistically increased numbers of mast cells in the mucosa (P <0.0001) and penetration of lanthanum nitrate through intercellular areas of the epithelium. Furthermore, the difference in mast cell counts between the high and therapeutic dose groups was also statistically significant (P <0.0001).: ConclusionsIndomethacin resulted in histopathologic findings typical of interstitial cystitis, such as leaky bladder epithelium and mucosal mastocytosis. The true incidence of nonsteroidal anti-inflammatory drug-induced cystitis in humans must be clarified by prospective clinical trials. [Copyright &y& Elsevier]

Abstract Aims The purpose of the present study was to investigate the potential antioxidant, anti-apoptotic and sperm function-preserving effects of estrogen, estrogen receptor (ER)α and ERβ agonists in a rat model of testis torsion-detorsion (T/D). Main methods Under anesthesia, 6–8-week-old male Sprague-Dawley rats underwent sham-operation or testicular torsion by fixing left testis rotated at 720° for 2 h. After detorsion, rats were treated with ERα agonist (1 mg/kg/day, subcutaneously, sc) or ERβ agonist (1 mg/kg/day, sc) or estradiol (E 2 , 1 mg/kg/day, in drinking water) or vehicle on the following two days. On the third day, testicular blood-flow was recorded and then left testes were extracted for molecular and histochemical analysis. Key findings The findings showed that reduced testicular blood-flow following torsion was partially restored on the 3rd day of detorsion, while treatments with either of the ER agonists or E 2 returned blood flow fully back to the control levels. When the testis-torsioned rats were given ERβ agonist during the detorsion period, tubular injury was lessened, sperm count and motility were increased, while the production of reactive oxygen metabolites and apoptosis in the testis tissues were totally suppressed. Although a down-regulated expression of androgen receptor (AR) along with a reduction in serum testosterone level was observed in the vehicle-treated T/D group, all three treatments up-regulated the expressions of AR and its mRNA, while ERα agonist and E 2 suppressed the testosterone level. Significance ERβ receptor activation during the post-ischemic period may be beneficial in protection against torsion-related oxidant testicular injury and infertility. Graphical abstract Unlabelled Image Highlights • Estrogen receptor (ER) ß agonist during the post-ischemic period decreased torsion-induced oxidant injury, apoptosis and tubular damage. • ERß agonist up-regulated the expressions of androgen receptor and its mRNA. • Abnormal sperm count and motility in the torsion group were improved by ERß treatment. • ERß receptor activation may protect against torsion-related infertility. [ABSTRACT FROM AUTHOR]

Highlights • Nesfatin-1 reduced pro-inflammatory cytokine expressions in torsioned rat testis. • Apoptosis and seminiferous tubular degeneration were depressed by nesfatin-1. • Nesfatin-1 elevated expressions of TGF-β and reduced AKT and CREB in testis. • Nesfatin-1 ameliorated oxidative damage and preserved spermatogenic cells. Abstract Testicular torsion causes ischemia-reperfusion injury and an increased risk of infertility. Nesfatin-1 is a novel peptide with antioxidant, anti-inflammatory and anti-apoptotic properties. In the present study, we aimed to investigate the putative beneficial effects of nesfatin-1 on oxidative injury and impaired testicular function induced by testis torsion. Under anesthesia, male Sprague-Dawley rats (180–230 g; n = 24) had sham-operation or they underwent testicular torsion by rotating the left testis 720° and fixing it for 2 h, followed by a 2-h detorsion. Rats in each group were treated intraperitoneally with either nesfatin-1 (0.3 μg/kg) or saline prior to the torsion or sham-torsion. At the end of the 4-h experimental period, tissue samples were removed for evaluation of spermatozoa, molecular and histochemical analyses. In saline-treated torsion/detorsion group, a high percentage of abnormal spermatozoa with head defects was observed, which was abolished in nesfatin-1-treated torsion/detorsion group. The levels of 8-OHdG, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, caspase-3 were increased in the saline-treated torsion/detorsion group as compared to sham-operated group, while nesfatin-1 pre-treatment significantly decreased the expressions of the pro-inflammatory cytokines, depressed apoptosis, and also reduced the tubular degeneration. In addition, nesfatin-1 in torsion/detorsion group elevated expressions of transforming growth factor (TGF)-beta and reduced expressions of protein kinase B (AKT) and cAMP response element binding protein (CREB) in the testis tissue. The present findings show that nesfatin-1, by regulating AKT and CREB signaling pathways and pro-inflammatory/anti-inflammatory cytokine balance, preserves the spermatogenic cells and ameliorates torsion-detorsion-induced tubular degeneration. [ABSTRACT FROM AUTHOR]

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels ( p < 0.05 ). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals ( p < 0.05 ). All parameters showed improvement in groups treated with ferulic acid ( p < 0.05 ). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound. [ABSTRACT FROM AUTHOR]

To evaluate the effects of exogenous ghrelin or obestatin on intestinal injury and accompanying pulmonary injury, intestinal ischemia–reperfusion (I/R) was induced in rats by obstructing the superior mesenteric artery for 60 min, whereas laparotomy was performed in the sham group. At the beginning of the 90-min reperfusion period, the rats were injected with obestatin (100 μg/kg), ghrelin (10 ng/kg), or saline intravenously (iv). At the end of reperfusion, the blood, ileum, and lung samples were taken for the histological and biochemical assays. In the saline-treated I/R group, the increased serum interleukin (IL)-1β level, high damage scores, and elevated tissue malondialdehyde level and collagen content in both tissues were significantly reduced by obestatin or ghrelin. Increased ileal myeloperoxidase activity of the saline-treated I/R group was reduced by treatment with obestatin or ghrelin, whereas increased pulmonary myeloperoxidase activity was reduced with administration of obestatin. Increased DNA fragmentation in the ileum of the saline-treated I/R group was reduced by both peptides. Elevated luminol–lucigenin chemiluminescence levels and nuclear factor kappa B (NF-κB) messenger RNA (mRNA) expression in the ileum of the saline-treated-I/R group were significantly decreased by obestatin or ghrelin treatment. I/R-induced depletion of the antioxidant glutathione in both ileal and pulmonary tissues was prevented with either obestatin or ghrelin treatment. Administration of either obestatin or ghrelin exerts similar protective effects against I/R-induced ileal and pulmonary injury, thus warranting further investigation for their possible use against ischemic intestinal injury. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nicotine and huperzine A treatments are beneficial in a rat model of acetic acid-induced colitis. [•] The mechanism is inhibition of oxidant production and release of pro-inflammatory cytokines. [•] Data suggest the role of the “anti-inflammatory cholinergic pathway” in this inflammatory condition. [ABSTRACT FROM AUTHOR]

Abstract: The cardioprotective effects of two different doses of erythropoietin administration were analyzed in rats with experimental myocardial infarction. None, saline, standard-dose (5000Ukg−1) and high-dose (10,000Ukg−1) of human recombinant erythropoietin alpha were administered intraperitoneally in Wistar rats with myocardial infarction induced by coronary artery ligation. Infarct sizes measured after triphenyltetrazolium chloride staining, levels of biochemical markers, histopathology examined by light and electron microscopy, and immunohistochemical expressions of erythropoietin, erythropoietin receptor, hypoxia inducible factor-1α and caspase-3, were analyzed. Lower scores of infarction and hemorrhage, lower number of macrophages and higher score of vascularization surrounding the infarct area were observed in the erythropoietin administered groups (p <0.05). Erythropoietin administration after myocardial infarction reduced the area of infarction and hemorrhage. There were hypoxia inducible factor-1α and caspase-3 expressions in the marginal area, and erythropoietin and erythropoietin receptor expression in both marginal and normal areas (p <0.001). Vascularization, erythropoietin expression in the normal area and vascular erythropoietin expression were positively correlated with human erythropoietin levels. The cardioprotective effects of erythropoietin treatment were independent of endogenous erythropoietin/erythropoietin receptor activity. Moreover exogenous erythropoietin treatment did not suppress endogenous erythropoietin. Erythropoietin administration after myocardial infarction reduced caspase 3 expression (apoptotic activity) and induced neovascularization around the infarct area. Higher erythropoietin administration did not provide an additional benefit over the standard-dose in myocardial protection. [Copyright &y& Elsevier]

Abstract: The aim of study was to investigate the fate and the morphology of the cells which constitute the spermatogenic line, and to determine the distribution of occludin in the testis in adult vasectomized Wistar rats. The rats were divided into two groups: control group (sham-operated) and vasectomized group. One, 3 and 6 months after sham and vasectomy operations, testis samples were examined. The weight of the testes was found to be reduced 3 and 6 months after vasectomy. There was vacuolization in the seminiferous tubules one month after vasectomy. The tubules showed severe atrophy 3 and 6 months after vasectomy. The occludin immunolabeling in the 3- and 6-month groups was weak and diffuse, and the density of the protein was found to be decreased. The increase in the number of apoptotic cells was accompanied by a time-dependent decrease in the number of haploid, diploid and tetraploid cells. This study demonstrated that vasectomy causes degeneration in the seminiferous tubules with alterations in occludin distribution with a decrease in the number of spermatogenic cells. Moreover, these alterations increase in a time-dependent manner. [Copyright &y& Elsevier]

Summary: Cysteinyl leukotrienes play a part in inflammatory reactions such as asthma and inflammatory bowel diseases. The leukotrienes exert their actions by binding to and activating various receptors. Montelukast, a leukotriene receptor antagonist, which is used in the treatment of asthma has been shown to be effective in inhibiting the action or formation of leukotrienes. Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and seem to be related to infiltration and activation of mast cells that are releasing vasoactive and pro-inflammatory mediators. The aim of the present study was to investigate the effects of montelukast on the degranulation of mast cells in the dermis that is induced by water avoidance stress (WAS). Wistar albino rats were divided into four groups of 8 animals each. Control rats were injected with (1) the vehicle solution or (2) the montelukast solution in the absence of WAS. (3) the WAS group of rats was administered vehicle solution following WAS exposure for 2h daily for 5 days. (4) The WAS+ML group was administered montelukast 10mg/kg; i.p. following WAS exposure for 2h daily for 5 days. Dermal mast cell numbers were determined with toluidine blue and tryptase immunohistochemistry and observed using a light microscope. Numbers of both granulated and degranulated mast cells were significantly increased in the WAS group when compared to control rats. Montelukast treatment decreased the number of both mature granulated and degranulated mast cells in rats subjected to WAS. In conclusion, chronic montelukast treatment reduced WAS-induced infiltration and activation of mast cells in the dermis and may provide a useful therapeutic option in stress-induced skin disorders. [Copyright &y& Elsevier]

Abstract: Gibberellic acid (GA3), a plant growth regulator, is used commonly in agriculture. Its potential hazardous effects on human health, however, were relatively unexplored. Several studies demonstrated that in animals chronic GA3 consumption increased tumor formation and oxidative stress. Mast cells and Substance P (SP) play an important role in inflammation. Because chronic inflammation triggers serious conditions, including tumor formation, we examined changes in mast cell recruitment and activation as well as SP levels in skin and urinary bladder. Wistar Albino rats were treated with either a single GA3 dose or multiple GA3 doses for 30 days. Sub-chronic exposure to GA3 markedly increased mast cell recruitment and activation in both tissues. Treatment with 2mg/kg GA3 dose for 30 days decreased SP levels in skin and bladder. SP levels returned to control values in bladder and further increased in skin following 30-day treatment with the 20mg/kg GA3 dose. There was marked urothelial loss and inflammatory cell infiltration in bladder of 30-day GA3 treated groups. In skin, single GA3 doses also decreased SP levels and enhanced mast cell activation and recruitment. Since both SP and mast cell activation elicit inflammatory responses, these results demonstrate that exposure to plant growth regulators may increase inflammatory skin and bladder disease and that use of GA3 should be clearly monitored. [Copyright &y& Elsevier]

Abstract: Clinical and experimental research findings suggest that a local burn insult produces oxidant-induced organ changes as evidenced by increased lipid peroxidation in lung, liver and gut. Adrenomedullin (AM), a potent vasodilator, was originally isolated from pheochromocytoma cells, and has been identified in other tissues. In this study, we investigated the potential role of AM in burn-induced remote organ damage in rats. Sprague–Dawley rats (250–300 g) were treated with either AM (100 ng/kg, subcutaneously) or saline 10 min before burn insult which covers 30% of total body surface area and were decapitated 24 h after the burn insult. Trunk blood was collected and analyzed for liver and kidney functions and for determination of TNF-α levels. The liver, lung and kidney samples were taken for histologic evaluation and for measurement of malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and chemiluminescence levels. The data revealed that AM treatment resulted in a significant protection in tissues tested against burn injury via suppression of lipid peroxidation, tissue neutrophil infiltration, oxidant generation and via decreasing circulating levels of the pro-inflammatory cytokine TNF-α. AM treatment was also effective in attenuating hepatic and kidney dysfunction due to burn injury, suggesting that peripherally AM administration may protect the tissues against burn-induced injury. [Copyright &y& Elsevier]

Abstract: Background: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. Objective: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). Methods: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content – an index of lipid peroxidation, and myeloperoxidase (MPO) activity – an index of neutrophil infiltration – were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-α, IL-1β and IL-6 were also assayed in plasma samples. Results: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p <0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p <0.05–p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. Conclusion: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. [Copyright &y& Elsevier]

Abstract: Background: Despite recent advances, severe burn is one of the most common problems faced in the emergency room. Major thermal injury induces the activation of an inflammatory cascade resulting in local tissue damage, to contribute to the development of subsequent damage of multiple organs distant from the original burn wound. Objective: Silymarin, the major component of milk thistle has been shown to have antioxidant properties. In the present study, we investigated the putative antioxidant effect of local or systemic silymarin treatment on burn-induced oxidative tissue injury. Methods: Wistar albino rats were exposed to 90°C bath for 10s to induce burn. Silymarin either locally (30mg/kg) applied on 4cm2 area or locally+systemically (50mg/kg, p.o.) was administered after the burn and repeated twice daily. Rats were decapitated 48h after injury and blood was collected for tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) activity. In skin tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol-lucigenin chemiluminescense (CL) were measured in addition to the histological evaluation. Results: Burn caused a significant increase in TNF-α and LDH levels. MDA levels were increased and GSH levels were decreased in the skin at 48h after-burn. Both local and systemic silymarin treatments significantly reversed these parameters. The raised MPO activity and luminol-lucigenin CL were also significantly decreased. Conclusion: Results indicate that both systemic and local administration of silymarin was effective against burn-induced oxidative damage and morphological alterations in rat skin. Therefore, silymarin merits consideration as a therapeutic agent in the treatment of burns. [Copyright &y& Elsevier]

Summary: We studied the potential effects of taurine, a free radical scavenger, on chronic water avoidance stress (WAS)-induced degeneration of the mucosa of the urinary bladder in experimental rats. Wistar albino rats were exposed to WAS for 2h/day, for 5 days (WAS group). Before exposing them to WAS, taurine (50mg/kg) (WAS+taurine group) was injected intraperitonally into the animals. Samples of urinary bladder were then investigated by light and scanning electron microscopy. Lipid peroxidation and gluthathione levels were also measured in the urinary bladder. In the WAS-only group, inflammatory cell infiltration, increased number of mast cells in the mucosa and ulcerated areas were observed. In the WAS+taurine group, relatively normal urothelial topography with microvilli, moderate inflammatory cell infiltration and decreased numbers of mast cells in the mucosa were observed. The increased lipid peroxidation and decreased glutathione levels in WAS rats were reversed by taurine treatment. We conclude that taurine protects against WAS-induced oxidant urinary bladder injury, and thus may be a possible therapeutic agent against interstitial cystitis, the symptoms of which are aggravated by stress conditions. [Copyright &y& Elsevier]

Abstract: Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective effect of montelukast, a CysLT1 receptor antagonist, against oxidative damage in a rat model of CRF, induced by 5/6 reduction of renal mass. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which received saline or montelukast (10mg/kg, i.p.) for 4 weeks. At the end of the 4 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples, while leukotriene B4, TNF-α, IL-1β, IL-6, total antioxidant capacity (AOC) and leukocyte apoptosis were assayed in plasma samples. Kidney, lung, heart and brain tissue samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, and the extent of tissue injuries was analyzed microscopically. CRF caused significant decreases in tissue GSH and plasma AOC, which were accompanied with significant increases in MDA levels, MPO activities, and collagen contents of all the studied tissues, while the circulating levels of the pro-inflammatory mediators, LDH activity, creatinine and BUN were elevated. Montelukast treatment reversed all these biochemical indices, as well as histopathological alterations induced by CRF. Similarly, flow cytometric measurements revealed that leukocyte apoptosis was increased in CRF group, while montelukast reversed this effect. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues, and that protective effects of montelukast on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and apoptosis, to balance oxidant-antioxidant status and to regulate the generation of pro-inflammatory mediators. [Copyright &y& Elsevier]

Summary: We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity. [Copyright &y& Elsevier]

Abstract: 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 (10mgkg−1 i.p.) for 15 days, and hypothyroidism was confirmed by depressed serum T3 and T4 concentrations. Under brief ether anesthesia, shaved dorsum of rats was exposed to 90°C (burn group) or 25°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)-α 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-α 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. [Copyright &y& Elsevier]