PHARMACOLOGICAL EVALUATION OF ZAFIRLUKAST IN EXPERIMENTALLY INDUCED GLOBAL CEREBRAL ISCHEMIA/REPERFUSION INJURY IN MICE


Bipin Kumar Nayak, Arun Kumar, Preeti Kothiyal

Abstract


Objective: Cysteinyl leukotrienes (CysLTs) are potent mediators of inflammation that are associated with cerebral ischemia/reperfusion (I/R) injury. The CysLTs receptor antagonist may offer protection against ischemic injury. The present study was designed to investigate the role of zafirlukast in experimentally induced global cerebral ischemia/reperfusion (I/R) injury in mice.

Methods: Global cerebral ischemia-reperfusion was induced by bilateral carotid artery occlusion for 17 min followed by 24 h reperfusion. Mice were randomly assigned to eight groups (n = 6 per group): control, sham-operated, I/R control, prednisolone treated group (5 mg/kg, p. o.) for 10 d, zafirlukast treated group (5, 10, 20 mg/kg, p. o.) for 10 d and combination group treated with zafirlukast (5 mg/kg, p. o.)+nifedipine (5 mg/kg, i. p.) for 10 d before ischemia/reperfusion. At the end of reperfusion (24 h), a blood sample was collected from retro-orbital route and mice’s brain was removed by cervical dislocation to measure serum lactate dehydrogenase (LDH), serum nitrite concentration, malondialdehyde (MDA), and cerebral infarct size.

Results: Zafirlukast showed the dose-dependent neuroprotective activity by a significant decrease in lipid peroxidation, lactate dehydrogenase, serum nitrite level and cerebral infarct size. The high dose of zafirlukast (20 mg/kg, p. o.) and combination of zafirlukast (5 mg/kg, p. o.) with nifedipine (5 mg/kg, i. p.) showed the most potent neuroprotective effect against ischemic/reperfusion (I/R) group.

Conclusion: This original study demonstrated the potency of zafirlukast in global cerebral ischemia/reperfusion injury. Also zafirlukast, in combination with nifedipine could represent a therapeutic approach to reduce inflammation associated with ischemia injury.


Keywords


Zafirlukast, Ischemia/reperfusion, Oxidative stress, Inflammation

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About this article

Title

PHARMACOLOGICAL EVALUATION OF ZAFIRLUKAST IN EXPERIMENTALLY INDUCED GLOBAL CEREBRAL ISCHEMIA/REPERFUSION INJURY IN MICE

Keywords

Zafirlukast, Ischemia/reperfusion, Oxidative stress, Inflammation

DOI

10.22159/ijpps.2018v10i2.21633

Date

01-02-2018

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 10, Issue 2, 2018 Page: 30-36

Online ISSN

0975-1491

Authors & Affiliations

Bipin Kumar Nayak
Division of Pharmaceutical Sciences, Shri Guru Ram Rai Institute of Technology & Science, Patel Nagar, Dehradun, Uttarakhand, India
India

Arun Kumar
Division of Pharmaceutical Sciences, Shri Guru Ram Rai Institute of Technology & Science, Patel Nagar, Dehradun, Uttarakhand, India
India

Preeti Kothiyal
Division of Pharmaceutical Sciences, Shri Guru Ram Rai Institute of Technology & Science, Patel Nagar, Dehradun, Uttarakhand, India
India


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