montelukast and Reperfusion-Injury

To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia.. Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups).. On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups.. The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.

Topics: Acetates; Acetylcysteine; Animals; Cyclopropanes; Kidney; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Succimer; Sulfides; Tomography, X-Ray Computed

Ischemia reperfusion injury is unavoidable in the setting of transplantation and may lead to primary dysfunction of the transplanted organ. Similarly, intestinal ischemia reperfusion injury may have deleterious effects causing intestinal failure. Montelukast is a selective reversible cysteinyl-leukotriene type 1 receptor antagonist used in clinical practice for its anti-inflammatory effects. In this study, we investigated the effects of Montelukast on colon anastomosis performed after intestinal ischemia reperfusion injury.. 40 adult male Wistar Albino rats were used. All rats underwent intestinal ischemia reperfusion injury. Afterwards, the entire group was divided into two for either right or left colonic resection and anastomosis. Rats in the control groups were given intra-peritoneal normal saline for 1 week while the animals in the treatment groups were given intra-peritoneal Montelukast (10 mg/kg; 1 ml). All animals were subjected to ischemia reperfusion injury followed by either right or left colonic segmental resection and anastomosis in the first day of the experiment. On postoperative day 7 adhesion scoring, anastomotic bursting pressure, anastomotic tissue hydroxyproline content were assessed for all groups.. Significant differences were detected in adhesion scores between the treatment and control groups regardless of the colonic resection site. Anastomotic bursting pressures and hydroxyproline content of the anastomotic sites were significantly higher in the treatment groups when compared with the control groups. Anastomotic tissues treated with Montelukast showed more prominent vascularization in histopathological examinations.. Montelukast has a potential to attenuate the detrimental effects of ischemia reperfusion injury on intestinal anastomosis.

Topics: Acetates; Anastomosis, Surgical; Animals; Colon; Cyclopropanes; Male; Quinolines; Rats, Wistar; Reperfusion Injury; Sulfides

Montelukast is a selective leukotriene D-4 receptor antagonist, which specifically and reversibly inhibits cysteinyl leukotriene-1 receptor. The aim of this study was to investigate the protective effect of Montelukast on skeletal muscle reperfusion injury created as acute ischemia-reperfusion (IR) injury in Wistar-albino rats.. The study comprised 16 male Wistar-albino rats. The rats were randomly separated into two groups as control (IR) and treatment (IR+Montelukast). Ischemia was obtained using a femoral artery clamp. After reperfusion following a 2-hour ischemia, muscle samples were taken for biochemical and histopathological analyses.. Malondialdehyde levels were determined to be at statistically higher levels in the control compared with that in the Montelukast group (p=0.002, p<0.01). The superoxide dismutase levels were determined to be at statistically higher level in the Montelukast group compared with that in the control group (p=0.001, p<0.01). In the histopathological examination of the ischemic muscles, edema, polymorinfiltration and erythrocyte extravasation levels were found to be statistically significant higher in the control group than in the Montelukast group. Edema, polymorphonuclear infiltration, and erythrocyte extravasation levels were observed to be significantly reduced in the treatment group compared with that in the control.. In this model of skeletal muscle acute IR injury, the protective effect of Montelukast against skeletal muscle reperfusion injury was emphasized. We concluded that Montelukast could accelerate functional recovery in the extremity by limiting the local and systemic complications caused by reperfusion in cases such as extremity trauma with vascular injuries and extremity surgery with prolonged tourniquet application. However, further experimental and clinical studies are required to confirm this effect.

Topics: Acetates; Animals; Cyclopropanes; Male; Malondialdehyde; Muscle, Skeletal; Protective Agents; Quinolines; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; Sulfides

Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to study the possible neuroprotective effect of Montelukast, a CysLTR1 antagonist in global cerebral ischemia/reperfusion (IR) injury in rats. Global cerebral ischemia-reperfusion was induced by bilateral carotid artery occlusion for 15 min followed by 60 min reperfusion period. Animals were randomly allocated into three groups (n = 30 per group): Sham operated, I/R control and rats treated with montelukast (0.5 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of montelukast. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid), Cys-LTs contents and CysLT1 receptor expression; as well as total brain infarct size and histopathological examination of the hippocampus were assessed. Montelukast protected hippocampal tissue by reducing oxidative stress, inflammatory and apoptotic markers. Furthermore, it reduced glutamate and lactate dehydrogenase activity as well as infarct size elevated by I/R. These results were consistent with the histopathological findings. Montelukast showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Topics: Acetates; Animals; Apoptosis Regulatory Proteins; Biomarkers; Cerebral Infarction; Cyclopropanes; Hippocampus; Inflammation Mediators; Ischemic Attack, Transient; Leukotriene Antagonists; Male; Neurotransmitter Agents; Oxidative Stress; Quinolines; Rats; Rats, Wistar; Receptors, Leukotriene; Reperfusion Injury; Sulfides

Paraplegia due to ischemia-reperfusion (I/R) injury of the spinal cord is a devastating complication of thoracoabdominal aortic surgery. Cysteinyl leukotrienes are potent mediators of inflammation that are associated with I/R injury. The present study was designed to investigate the role of montelukast, a selective reversible CysLT1 receptor antagonist, on spinal cord I/R injury in an experimental model.. Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion and montelukast administration), G2 (45 min. aortic occlusion; no montelukast administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast administration). After neurologic evaluation using the Motor Deficit Index (MDI) score at the 48th hour of reperfusion, lumbar spinal cords were removed for histopathological evaluation and immunohistochemical staining for HSP70, interleukin-6 and myeloperoxidase (MPO).. All rats in the G1 group had a normal neurological status and their MDI score was 0 (p < 0.05). The MDI score of G3 was significantly lower than G2 group (2.8 vs. 5.5; p < 0.05). Vacuolar congestion was found to be significantly lower in G1 than the other groups (p=0.0001). The interleukin-6 receptor level was found to be significantly lower in G3 group than the control group (p=0.013). There was no statistically significant difference found among the groups in terms of the degree of HSP70 and MPO staining.. Increased generation of leukotrienes in postischemic organs play an important role in I/R injury. The findings of the current study demonstrated that montelukast improved motor recovery and decreased IL-6 levels in spinal cord I/R injury.

Topics: Acetates; Animals; Cyclopropanes; Interleukin-6; Leukotriene Antagonists; Male; Neuroprotective Agents; Paraplegia; Peroxidase; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, Leukotriene; Reperfusion Injury; Spinal Cord Ischemia; Sulfides

Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats.

Topics: Acetates; Acute-Phase Proteins; Alanine Transaminase; Animals; Aspartate Aminotransferases; Caspase 8; Caspase 9; Cyclopropanes; Interleukin-6; Intestinal Mucosa; Kidney; Lipocalin-2; Lipocalins; Liver; Male; Protective Agents; Proto-Oncogene Proteins; Quinolines; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, Leukotriene; Reperfusion Injury; RNA, Messenger; Sulfides; Tumor Necrosis Factor-alpha

To investigate the efficacy of montelukast for prevention of ischaemia/reperfusion (I/R) injury in rat ovary.. Twenty-four female adult rats were included in the study. I/R injury was induced by CO2 pneumoperitoneum in a laparoscopic rat model. The rats were divided at random into three groups: the sham group was subjected to catheter insertion but was not subjected to pneumoperitoneum; the saline group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 1 mg/kg physiological saline administered 10 min before pneumoperitoneum; and the montelukast group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 20mg/kg montelukast administered 10 min before pneumoperitoneum. Damage to ovarian tissue was scored by histopathological evaluation. Caspase-3 expression was determined immunohistochemically. Ovarian tissue levels of malondialdehyde and glutathione, and plasma total antioxidant capacity were measured biochemically.. In comparison with the sham group, ovarian sections in the montelukast group had higher scores for follicular degeneration and oedema (p<0.001). Montelukast treatment prevented tissue damage in ovaries, and this result was significant. Caspase-3 expression was only observed in ovarian surface epithelium in the saline and montelukast groups. However, the mean caspase-3 expression score was higher in the saline group than the montelukast group (p<0.001). Tissue levels of malondialdehyde were higher in the montelukast group than the sham group, but plasma total antioxidant capacity and tissue levels of glutathione were significantly lower. Pretreatment with montelukast reduced lipid peroxidation (p<0.005) and improved antioxidant status in rats (p<0.001).. Montelukast is effective for the prevention of I/R-induced damage in rat ovary.

Topics: Acetates; Animals; Caspase 3; Cyclopropanes; Female; Glutathione; Leukotriene Antagonists; Lipid Peroxidation; Malondialdehyde; Ovary; Pneumoperitoneum, Artificial; Quinolines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sulfides

To evaluate the effects of montelukast and Hypericum perforatum against ischemia/reperfusion (I/R)-induced intestinal damage.. Twenty-eight hamsters were divided into 4 groups following midline abdominal laparotomy: control group (n = 7), I/R group (n = 7), montelukast and I/R (MIR) group (n = 7), and Hypericum perforatum and I/R (HPIR) group (n = 7). After 60 min of ischemia through obstruction of the superior mesenteric artery, 24 h of reperfusion was maintained. Ten minutes prior to the reperfusion period, the MIR group received 7 mg/kg of intraperitoneal montelukast and the HPIR group received 7 mg/kg of intraperitoneal Hypericum perforatum. Malondialdehyde, glutathione, myeloperoxidase, and cardiotrophin-1 levels were measured from blood samples. A semiquantitative histological evaluation was performed.. Montelukast and Hypericum perforatum significantly reduced malondialdehyde levels and increased glutathione levels compared to the I/R group (P < 0.008). A statistically significant difference was also found between the I/R group and MIR and HPIR groups in terms of myelqperoxidase levels (P < 0.008). The MIR and HPIR groups showed increased cardiotrophin- 1 levels compared to the control and I/R groups (P < 0.008 for all). The MIR and HPIR groups showed significantly lower histological scores compared to the I/R group (P = 0.03 and P = 0.007, respectively).. This study demonstrated the preventive effects of montelukast and Hypericum perforatum on I/R-induced intestinal injury.

Topics: Acetates; Animals; Cricetinae; Cyclopropanes; Disease Models, Animal; Glutathione; Hypericum; Intestines; Malondialdehyde; Mesenteric Artery, Superior; Mesocricetus; Plant Extracts; Protective Agents; Quinolines; Random Allocation; Reperfusion Injury; Sulfides

The thoracic or thoracoabdominal aortic aneurysm surgery may cause spinal cord ischemia because of aortic cross-clamping and may result in severe postoperative complications caused by spinal cord injury. Ischemia/reperfusion injury may directly or indirectly be responsible for these complications. In this study we sought to determine whether combination of iloprost and montelukast can reduce the ischemia/reperfusion injury of spinal cord in a rat model.. Medulla spinalis tissue concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO) and heat shock protein 70 (HSP-70) were determined in 3 groups of Spraque Dawley rats: control group (operation with cross clamping and intraperitoneal administration of 0.9% saline, n = 7), sham group (operation without cross clamping, n = 7), and study group (operation with cross-clamping and intraperitoneal administration of iloprost (25 ng/kg) and montelukast (1 mg/kg), n = 7). The abdominal aorta was clamped for 45 minutes, with a proximal (just below the left renal artery) and a distal (just above the aortic bifurcation) clip in control and study groups. Hindlimb motor functions were evaluated at 6, 12, 24, and 48 hours using the Motor Deficit Index score. All rats were sacrificed 48 hours after the procedure and spinal cord tissue levels of myeloperoxidase, interleukin-6, and heat shock protein (HSP-70) were evaluated as markers of oxidative stress and inflammation. Histopathological analyses of spinal cord were also performed.. The tissue level of HSP-70 was found to be similar among the 3 groups, however, MPO was highest and IL-6 receptor level was lowest in the control group (p = 0.007 and p = 0.005; respectively). In histopathological examination, there was no significant difference among the groups with respect to the neuronal cell degeneration, edema, or inflammation, but vascular congestion was found to be significantly more prominent in the control group than in the sham or in the study group (p = 0.05). Motor deficit index scores at 24 and 48 hours after ischemia were significantly lower in the study group than in the control group.. This study suggests that combined use of iloprost and montelukast may reduce ischemic damage in transient spinal cord ischemia and may provide better neurological outcome.

Topics: Acetates; Animals; Biomarkers; Cyclopropanes; Drug Administration Schedule; Drug Therapy, Combination; Iloprost; Injections, Intraperitoneal; Male; Neuroprotective Agents; Oxidative Stress; Quinolines; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spinal Cord; Spinal Cord Injuries; Sulfides; Treatment Outcome

The aim of this study was to examine whether treatment with montelukast, a selective leukotriene antagonist, would affect anastomotic healing in a reperfused colon rat model with remote ischemia/reperfusion injury.. Rats (n = 12 per group) were intraperitoneally administered normal saline or 10 mg/kg montelukast sodium 60 minutes before and for 5 days after surgery. Ischemia was induced for 45 minutes through superior mesenteric artery occlusion. A left colon anastomosis was made. Blood and perianastomotic tissue samples were obtained on postoperative day 5.. Mean anastomotic bursting pressures of the control and montelukast groups were 159.17 ± 29.99 and 216.67 ± 26.40, respectively (P < .001). Compared with saline, montelukast treatment increased the mean tissue hydroxyproline level (2.46 ± .30 vs 3.61 ± .33 μmol/L) and decreased tissue caspase-3 activity (36.06 ± 5.72 vs 21.78 ± 3.87) and malondialdehyde levels (3.43 ± .34 vs 2.29 ± .34 nmol/g) (P < .001 for all). Other plasma markers of injury also showed differences.. Montelukast prevented ischemia/reperfusion-induced damage in a rat model of colonic anastomotic wound healing.

Topics: Acetates; Alanine Transaminase; Anastomosis, Surgical; Animals; Aspartate Aminotransferases; Caspase 3; Catalase; Colon; Cyclopropanes; Glutathione; Hydroxyproline; Interleukin-6; Leukotriene Antagonists; Lipid Peroxidation; Male; Malondialdehyde; Models, Animal; Nitric Oxide; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Sulfides; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Wound Healing

Ischemia-reperfusion (I/R) event in vascular and nervous system has been documented to rising ischemic and vasculitic neuropathic pain, clinically resembles the complex regional pain syndrome (CRPS). The present study evaluated the effect of montelukast, a cysteinyl leukotriene receptor (Cys-LTC(4) and Cys-LTD(4)) antagonist on ischemia -reperfusion (I/R) induced vasculitic neuropathic pain in rats.. Behavioral parameters were assessed at different time intervals (i.e. 0, 1, 7, 14 and 21st day) and biochemical analysis in sciatic nerve tissue samples were also performed along with histopathological studies.. Behavioral pain assessment has shown increase in paw and tail withdrawal threshold in montelukast treated groups against thermal and mechanical stimuli as compared to I/R control group. We observed a decrease in the total calcium, thiobarbituric acid reactive substance (TBARS) and myeloperoxidase (MPO) activity levels, whereas there is rise in reduced glutathione level in montelukast treated groups as compared to I/R control group. However, significant behavioral and biochemical results were observed only in medium and high dose of treated groups which were comparable to normal control group. Moreover, histopathological study has revealed the reduction of I/R induced neuronal edema and axonal degeneration due to montelukast.. Montelukast has ameliorated I/R induced vasculitic neuropathic pain, these effects may be due to inhibition of lipid peroxidation, reduction of oxidative stress, release of inflammatory mediators and neuroprotective actions. Hence, it could be used as a novel therapeutic agent for the management of vasculitic inflammation related neuropathic pain.

Topics: Acetates; Animals; Behavior, Animal; Calcium; Cyclopropanes; Glutathione; Hot Temperature; Immersion; Leukotriene Antagonists; Neuralgia; Pain Measurement; Peroxidase; Physical Stimulation; Quinolines; Rats; Rats, Wistar; Reaction Time; Reperfusion Injury; Sciatic Nerve; Sulfides; Thiobarbituric Acid Reactive Substances; Vasculitis

To reveal the effects of montelukast as an antioxidant and tissue protective agent and study the biochemical and histopathologic changes in experimental ischemia and ischemia-reperfusion (I/R) injury in rat ovaries.. Experimental study.. Experimental surgery laboratory in a university department.. Forty-eight rats with experimentally induced ovarian torsion.. Group 1: sham; Group 2: ovarian ischemia; Group 3: a 30-hour period of ischemia followed by a 3-hour reperfusion. Groups 4 and 5: rats administered 10 and 20 mg/kg doses of montelukast before a half-hour of ischemia, then ovarian ischemia applied; after a 3-hour period of ischemia, the bilateral ovaries removed. Groups 6 and 7: 3-hour period of ovarian ischemia applied, then 2.5 hours after the ischemia induction, rats given montelukast. Group 8: sham operation and 20 mg/kg of montelukast; at the end of a 3-hour period of ischemia, 3-hours of reperfusion continued.. Measurement of ovarian tissue concentrations of superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO) and myeloperoxidase (MPO) activity; and histopathologic examination of all ovarian rat tissue.. Montelukast treatment normalized changes of LPO and MPO and stimulated an overproduction of endogenous SOD and GSH. The results of the histologic parameters showed that treatment with montelukast in the I/R group of rats ameliorated the development of ischemia and reperfusion tissue injury.. Montelukast at different doses attenuates ovarian I/R-induced ovary tissue injury in rats.

Topics: Acetates; Animals; Antioxidants; Cyclopropanes; Female; Ovarian Diseases; Oxidative Stress; Protective Agents; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Sulfides

Ischemia and reperfusion (I/R) injury is characterized by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on hepatic I/R injury in rats. Wistar albino rats through clamping hepatic artery, portal vein, and bile duct, were subjected to 45 min of hepatic ischemia followed by 60 min reperfusion period. Montelukast (10 mg/kg; i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period, the rats were killed by decapitation. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (TNF-alpha and IL-1beta) were determined in blood samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) and Na+, K+-ATPase activities were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities were elevated in the I/R group, while this increase was significantly decreased by montelukast treatment. Hepatic GSH levels and Na+, K+-ATPase activity, significantly depressed by I/R, were elevated back to control levels in montelukast-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels, and MPO activity due to I/R injury were reduced back to control levels with montelukast treatment. Since montelukast administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that montelukast with its anti-inflammatory and antioxidant properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.

Topics: Acetates; Animals; Cyclopropanes; Cytokines; Glutathione; Leukotriene Antagonists; Liver; Liver Diseases; Liver Function Tests; Male; Malondialdehyde; Peroxidase; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Sulfides

Hepatic ischemia-reperfusion injury (I/R) may occur in transplantation, trauma, and elective hepatic resections. Leukotrienes have been shown to play a major role in hepatic I/R injury. Five-lipoxygenase enzyme is an important enzyme in the production of leukotrienes from arachidonic acid. MK-886 is an inhibitor of 5-lipoxygenase, and montelukast is a cysteinyl leukotriene receptor antagonist. The aim of this study was to investigate whether MK-886 and montelukast are effective in preventing hepatic I/R injury.. Rats were divided into five groups consisting of seven rats in each: (1) Control I/R, (2) Control-montelukast, (3) Control-MK-886, (4) I/R+montelukast, and (5) I/R+MK-886. Thirty min of total hepatic vascular occlusion and then 60 min reperfusion were performed to animals in groups 1, 4, and 5. In groups 2 and 4, montelukast, and in groups 3 and 5, MK-886 was applied intraperitoneally before and during the surgical procedures.. Apoptosis in the liver and intestine decreased significantly in the I/R+montelukast and I/R+MK-886 groups compared with the I/R group. Tissue malondialdehyde levels and glutathione consumptions also decreased significantly in the I/R+montelukast and I/R+MK-886 groups compared with the I/R group. The difference in serum alanine aminotransferase and aspartate aminotransferase levels between the groups did not reach significance.. Montelukast and MK-886 were found to be effective in prevention of liver and intestine injury by reducing apoptosis and oxidative stress in a hepatic I/R model. Anti-inflammatory properties and inhibition of lipid peroxidation by montelukast and MK-886 could be protective for these organs in I/R injury.

Topics: Acetates; Animals; Cyclopropanes; Disease Models, Animal; Indoles; Leukotriene Antagonists; Lipoxygenase Inhibitors; Liver Diseases; Male; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Sulfides

Recent studies have shown that neutrophils play an important role in the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether the administration of montelukast sodium, a selective reversible cysteinyl leukotriene 1 (CysLT1) receptor antagonist, decreases neutrophil infiltration and promotes flap survival.. Eighteen rats were used and randomly divided into three groups (n=6 for each group). Group I was the sham group and did not undergo ischemic insult; rather, normal saline (1 mL) was administrated intraperitonealy (i.p.) 30 min before surgery and continued for 6 d. Group II (control) and Group III (montelukast) underwent 12 h of ischemic insult. For Group II, normal saline (1 mL) was injected i.p. 30 min before the surgery and immediately before reperfusion, and this continued for 6 d. In Group III, 1 mL of montelukast (10mg/kg) was injected i.p. and continued for 6 d. Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) enzyme activities were investigated. Histological evaluation was made to investigate the tissue neutrophil count. Survival areas were assessed at 7 d postoperatively.. Group III (montelukast- treated) showed a significantly higher survival rate than Group II (control) (P=0.029) but a lower survival rate than Group I (sham). Histological and biochemical assays corroborated this data.. This study suggests that montelukast CysLT1 receptor antagonist montelukast reversed I/R-induced oxidant responses and improved flap survival by inhibiting neutrophil infiltration and balancing oxidant and antioxidant status.

Topics: Acetates; Animals; Cell Movement; Cyclopropanes; Glutathione; Graft Survival; Injections, Intraperitoneal; Leukotriene Antagonists; Male; Malondialdehyde; Models, Animal; Neutrophils; Peroxidase; Quinolines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Skin Transplantation; Sulfides; Surgical Flaps; Treatment Outcome

The present study aimed to investigate the possible beneficial effects of the cysteinyl leukotriene-1 receptor antagonist montelukast on contractility and oxidant damage after ischaemia/reperfusion (I/R) of rat urinary bladder. The abdominal aorta of Sprague-Dawley rats was occluded to induce I/R. Montelukast (10 mg kg(-1)) or saline was administered intraperitoneally before I/R. In the sham-operated group, the abdominal aorta was left intact and the animals were treated with montelukast or saline. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for biochemical assays. In the I/R group, the isometric contractile responses of the bladder strips to carbachol (10(-8)-10(-4) M) were lower than those of the control group and were reversed by treatment with montelukast. Lipid peroxidation and myeloperoxidase activity of the bladder tissues in the I/R group were greater than in the sham-operated group. Montelukast treatment in the I/R group decreased these parameters compared with I/R alone. Similarly, the significant decrease in tissue glutathione level in the I/R group compared with controls was also prevented by montelukast. Treatment with montelukast almost completely reversed the low contractile responses of rat urinary bladder to carbachol and prevented oxidative tissue damage following I/R.

Topics: Acetates; Animals; Cyclopropanes; Female; Glutathione; Isometric Contraction; Leukotriene Antagonists; Lipid Peroxidation; Male; Muscle, Smooth; Oxidative Stress; Peroxidase; Quinolines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sulfides; Urinary Bladder; Urinary Bladder Diseases

Oxygen free radicals are important components involved in the pathophysiological processes observed during ischemia/reperfusion (I/R).. 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.. 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.. 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.. 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.

Topics: Acetates; Animals; Blood Urea Nitrogen; Creatinine; Cyclopropanes; Glutathione; Interleukin-1; Interleukin-6; Kidney; L-Lactate Dehydrogenase; Leukotriene Antagonists; Leukotriene B4; Male; Malondialdehyde; Neutrophil Infiltration; Peroxidase; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Sulfides; Tumor Necrosis Factor-alpha