montelukast and Burns

Burns are severe injuries often associated with impaired wound healing. Impaired healing is caused by multiple factors, including dysregulated inflammatory responses at the wound site. Interestingly, montelukast, an antagonist for cysteinyl leukotrienes and U.S. Food and Drug Administration approved for treatment of asthma and allergy, was previously shown to enhance healing in excision wounds and to modulate local inflammation.. In this study, the authors examined the effect of montelukast on wound healing in a mouse model of scald burn injury. Burn wound tissues isolated from montelukast- and vehicle-treated mice at various times after burn injury were analyzed for wound areas ( n = 34 to 36), reepithelialization ( n = 14), inflammation ( n = 8 to 9), and immune cell infiltration ( n = 3 to 6) and proliferation ( n = 7 to 8).. In contrast to previously described beneficial effects in excision wounds, this study shows that montelukast delays burn wound healing by impairing the proliferation of keratinocytes and endothelial cells. This occurs largely independently of inflammatory responses at the wound site, suggesting that montelukast impairs specifically the proliferative phase of wound healing in burns. Wound healing rates in mice in which leukotrienes are not produced were not affected by montelukast.. Montelukast delays wound healing mainly by reducing the proliferation of local cells after burn injury.. Although additional and clinical studies are necessary, our study suggests that burn patients who are on montelukast may exhibit delayed healing, necessitating extra observation.

Topics: Acetates; Animals; Burns; Cyclopropanes; Endothelial Cells; Inflammation; Leukotrienes; Mice; Quinolines; Sulfides; Wound Healing

Montelukast, a selective cysteinyl leukotriene D4-receptor antagonist, is used in the treatment of asthma. In a rat model, our aim was to investigate the effects of montelukast, alone or in combination with topical antibiotics, on local burn wound healing.. Rats were randomly allocated to four groups after local burn development: Group 1; rats were left to secondary healing without treatment, Group 2; a dose of 10 mg/kg montelukast was given by gastric gavage once a day for 10 days, Group 3; rats were treated with topical pomade (bacitracin neomycin sulphate), and Group 4; rats were treat with a combination of topical antibiotic and montelukast (10 mg/kg were given by gastric gavage once a day for 10 days). Skin biopsies were taken on days 3, 10, 14, and 20 relative to burn induction.. Reepithelialization in the pomade and montelukast+pomade groups on the 10th day was significantly greater, in comparison with control and montelukast groups (p < 0.05). For the montelukast group, edema (on the 14th day) and angiogenesis, fibroblast proliferation, edema and macrophage infiltration (on the 20th day) were statistically improved in comparison with the control group (p < 0.05). For the montelukast+pomade group, angiogenesis, fibroblast proliferation and macrophage infiltration (on the 10th day), and angiogenesis, fibroblast proliferation, edema and macrophage infiltration (on the 14th and 20th days) were statistically improved in comparison with the control group (p < 0.05).. In conclusion, montelukast was effective on burn wound healing. Moreover, the effect was amplified when combined with topical antibiotics applied in the early stage of burn wound healing.

Topics: Acetates; Animals; Anti-Bacterial Agents; Burns; Cyclopropanes; Leukotriene Antagonists; Male; Neutrophil Infiltration; Quinolines; Random Allocation; Rats; Rats, Sprague-Dawley; Sulfides; Wound Healing

There is increasing evidence that oxidative stress has an important role in the development of multiorgan failure after major burn injury. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced injury of the gut. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the skin samples, as well as tissue samples from stomach, ileum and colon, were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum TNF-alpha and LDH were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced gastrointestinal damage and protects against oxidative injury by a neutrophil-dependent mechanism.

Topics: Acetates; Animals; Biomarkers; Burns; Cyclopropanes; Glutathione; Intestines; L-Lactate Dehydrogenase; Leukotriene Antagonists; Malondialdehyde; Neutrophils; Oxidative Stress; Quinolines; Rats; Rats, Wistar; Skin; Sulfides; Tumor Necrosis Factor-alpha

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

Topics: Acetates; Animals; Blood Urea Nitrogen; Burns; Cyclopropanes; Enzymes; Female; Glutathione; Kidney; Leukotriene Antagonists; Liver; Lung; Male; Malondialdehyde; Neutrophils; Oxidative Stress; Quinolines; Rats; Rats, Wistar; Skin; Sulfides; Tumor Necrosis Factor-alpha