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Objective Cysteinyl leukotrienes are potent inflammatory mediators. Their actions are mediated by specific receptors,the CysLT receptors(CysLT1R and CysLT2R),which have been cloned and characterized. In this stud-y,we investigated the protective effects of the CysLTR antagonist Pranlukast and HAMI 3379 on global cerebral ischemia/reperfusion(CI/R)injury in gerbils and its underlying mechanisms. Methods The gerbil model of CI/R was established by bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion. Then the animals were equally ran-domized into four groups: sham, model, Pranlukast(0.1 mg/kg)and HAMI 3379(0.1 mg/kg)groups. The later two groups were treated with intraperitoneal injection of Pranlukast and HAMI 3379,respectively,once daily for 4 days before carotid artery occlusion,while the former two groups with saline only,all at 10 mL/kg. After 24 h reperfusion,neurologi-cal deficit scores were observed and the behavioral dysfunction was assessed. The neuron morphology of cerebral cortex and CA1 subregion of hippocampus were observed in brain sections stained with cresyl violet. The expression of autophagy-relat-ed proteins beclin-1 and LC3 in the homogenate of cerebral cortex and hippocampus were determined using western blotting analysis. The ultrastructure of autophagosomes in the CA1 subregion of hippocampus was observed by electron microscopy. Results Compared with the model group, Pranlukast and HAMI 3379 attenuated neurological deficits, improved the be-havioral dysfunction,inhibited the neuron injury and loss, decreased the expression of autophagy-related protein beclin-1 and LC3 and the number of autophagosomes. Conclusions cysteinyl Leukotriene receptor antagonist Pranlukast and HAMI 3379 can alleviate global cerebral ischemia/reperfusion injury in gerbils. The protective effects of Pranlukast and HAMI 3379 appear to be associated with the inhibition of autophagy.
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BACKGROUND: Leukotriene receptor antagonists have been used to prevent virus-induced asthma exacerbations in autumn. Its efficacy, however, might differ with age and sex. OBJECTIVE: This study aimed to investigate whether pranlukast added to usual asthma therapy in Japanese children during autumn, season associated with the peak of asthma, reduces asthma exacerbations. It was also evaluated the effect of age and sex on pranlukast's efficacy. METHODS: A total of 121 asthmatic children aged 1 to 14 years were randomly assigned to receive regular pranlukast or not according to sex, and were divided in 2 age groups, 1–5 years and 6–14 years. The primary outcome was total asthma score calculated during 8 weeks by using a sticker calendar related to the days in which a child experienced a worsening of asthma symptoms. This open study lasted 60 days from September 15 to November 14, 2007. RESULTS: Significant differences in pranlukast efficacy were observed between sex and age groups. Boys aged 1 to 5 years had the lower total asthma score at 8 weeks (p = 0.002), and experienced fewer cold episodes (p = 0.007). There were no significant differences between pranlukast and control group in total asthma score at 8 weeks (p = 0.35), and in the days in which a child experienced a worsening of asthma symptoms (p = 0.67). CONCLUSION: There was a substantial benefit of adding pranlukast to usual therapy in asthmatic children, especially in boys aged 1 to 5 years, during autumn season.
Subject(s)
Child , Child, Preschool , Humans , Asian People , Asthma , Leukotriene Antagonists , SeasonsABSTRACT
OBJECTIVE To investigate the effect of pranlukast(Pran) on learning and memory impairment and neuroinflammatory and apoptotic response in streptozocin(STZ)-induced type 1 diabetic mice. METHODS Male ICR mice were injected through the tail vein with STZ(150 mg·kg-1)to induce the type 1 diabetes model. Diabetic mice were administered orally with Pran. After 4 consecutive weeks of administration,the escape latency in hidden platform trials,number of platform crossings and time spent in the target quadrant of mice were assessed by the Morris water maze(MWM)test. Western blot was used to detect the proteins of cysteinyl-leukotrienes receptor-1(CysLT1R)and pro-inflammatory factors,nuclear factor-κB p65 subunit(NF-κB p65),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and cleaved caspase 3,Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice. We also determined fasting blood glucose,serum insulin and lipids such as triglyceride,total cholesterol,high density lipoprotein cholesterol,and low density lipoprotein cholesterol. RESULTS The data of the MWM test showed that untreated diabetic mice displayed a higher escape latency in hidden platform trials(P<0.05),and a smaller number of platform crossings(P<0.05)as well as shorter per?centage of time spent in the target quadrant(P<0.05). The data of Western blotting showed that treat?ment with Pran 0.6 and 1.2 mg·kg-1 significantly reduced the levels of CysLT1R,nuclear NF-κB p65, IL-1βand TNF-α,cleaved caspase 3,and the ratio of Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice(P<0.05). However,Pran did not improve the fasting blood glucose,serum insulin or lipid metabolism disorder in diabetic mice. CONCLUSION Pran improves memory impairment and nerve injury in STZ-induced type 1 diabetic mice.
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Leukotriene receptor antagonists, which are generally considered safe with a few adverse drug reactions, are increasingly used in the treatment of various allergic diseases, including asthma and allergic rhinitis. Although a few anaphylactic reactions to montelukast have been reported worldwide, there is still a lack of reports about severe adverse drug reactions associated with pranlukast. Here, we report a case of severe hypersensitivity reaction associated with pranlukast. A 65-year-old woman developed anaphylactic shock that presented as generalized urticaria, angioedema, collapse, and loss of consciousness after receiving pranlukast. A positive response to oral challenge and skin prick testing with pranlukast was observed in the patient. In this case, it was demonstrated that pranlukast can induce anaphylaxis, possibly mediated by the IgE-dependent pathway.
Subject(s)
Aged , Female , Humans , Anaphylaxis , Angioedema , Asthma , Drug-Related Side Effects and Adverse Reactions , Hypersensitivity , Leukotriene Antagonists , Rhinitis , Skin , Unconsciousness , UrticariaABSTRACT
Objective To investigate whether leukotriene D4 (LTD4) regulates eotaxin-3 (Eot-3) expression in bronchial epithelial cells, and study effect of pranlukst on the regulation.Methods BEAS-2B cells and normal human bronchial epithelia cells were pre- treated with LTD4 for 1 hour,stimulated with interleukin-4, the cells were incubated for 24 hours. Eot-3 protein in supernatant were measured by enzyme linked immunosorbent assay(ELISA). The cells were pretreated with pranlukast in different concentration, then the above procedure was repeated. Results The untreated bronchial epithelial cell expressed Eot-3 protein on a very low level. After stimulating with IL-4 and incubating for 24 hours, Eot-3 production increased significantly. Pretreating the cells with LTD4 enhanced the inducing effect of IL-4. Pranlukast inverted the upregulation of LTD4. Conclusions Upregulating the expression of Eot-3 induced by IL-4 on bronchial epithelial cells may explain partially the mechanism of leukotrienes involving airway allergic inflammation of asthma. The invertion impact on upregulation of LTD4 by pranlukast may be one of mechanisms that leukotrienes receptor antagonist cure asthma.
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Aim To determine whether pranlukast (ONO-1078), a cysteinyl leukotriene receptor antagonist, possesses therapeutic effect when administered after focal cerebral ischemia in mice. Methods Persistent focal cerebral ischemia was induced by middle cerebral artery occlusion. Pranlukast and edaravone, a positive control drug, were ip injected 1, 6 and 24 h after ischemia. The neurological deficits were evaluated by neurological scores and inclined plane test 24 and 48 h after the surgery. Forty-eight h later, the brain slices were prepared for measurements of infarct volume and the ratio of ischemic/non-ischemic hemispheres. Brain sections were cut and examined for neuron densities in different regions of the brain. The effects of pranlukast and edaravone were evaluated by the changes of these variables. Results Pranlukast (0.1 and 0.2 mg?kg -1) and edaravone (3 and 10 mg?kg -1) significantly reduced the neurological deficits, infarct volume (maximally 82.3%), ratio of ischemic/non-ischemic hemispheres, and attenuated the reduction of neuron densities in hippocampal CA1 region, cortex and striatum. Conclusion Pranlukast possesses therapeutic effect on ischemic insults when administered after ischemia as effective as edravone, indicating a therapeutic potential in the treatment of ischemic stroke.
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BACKGROUND AND OBJECTIVE: The cysteinyl leukotrienes are bioactive lipid mediators that contribute to the pathophysiologic condition of asthma and rhinosinusitis. We tested whether the leukotriene receptor antagonist ONO-1078 (Pranukast) had steroid sparing effect on mode- rate to severe asthmatics with chronic rhinosinusitis. METHODS: Eighteen asthmatic patients with chronic rhinosinusitis who required more than 800 mcg/day of budesonide inhalation for the adequate control of asthma symptoms were recruited for this study. For the first 4 weeks, patients were treated with high dose (800-1200 mcg/day) budesonide inhalation. For the next 4 weeks, the dose of budesonide inhalation was decreased by 400 mcg/day and oral ONO-1078 (900mg/day) was administered. FEV1 was evaluated every 2 weeks, and PC20 on methacholine challenge, serum eosinophil cationic protein and blood eosinophil count were measured every 4 weeks. Diary cards were completed with morning and evening PEFR and symptom scores for asthma and rhinosinusitis during the treatment periods. RESULTS: Despite the reduction of the dose of inhaled corticosteroid by 400mcg/day, FEV1 and PEFR did not decrease with the addition of oral ONO-1078. The symptom scores of asthma and rhino-sinusitis did not change, and the need for beta2-agonist did not increase. CONCLUSION: These results suggest that ONO-1078 might have steroid sparing effect in moderate to severe persistent asthmatics with chronic rhinosinusitis who required high dose nhaled budesonide to control asthma symptoms.