Neuroprotective effect of allopurinol and nimesulide against cerebral ischemic reperfusion injury in diabetic rats

M.A. Ansari, S.K. Hussain, M.P. Mudagal, D. Goli

Department of Pharmacology, Acharya and B.M. Reddy College of Pharmacy, Soldevanhalli, Bangalore, India. mohdasif@acharya.ac.in

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• Pharmacology

OBJECTIVES: The main objective of the study was to determine the neuroprotective effect of allopurinol and nimesulide against the cerebral ischemic reperfusion injury in diabetic and nondiabetic rats.

MTERIALS AND METHODS: In this study, Wistar albino rats of either sex weighing 150-250 g were procured from authorized suppliers. Rats were anesthetized by giving thiopentone sodium (45 mg/kg) by i.p. Under anesthesia, midline incision was given. Common carotid arteries were identified and isolated carefully from vago-sympathetic nerve. Rats were made ischemic by occluding bicommon carotid arteries with thread for 30 min, followed by reperfusion for 4 h by removing the occlusion. The drugs allopurinol (15, 30 mg/kg) and nimesulide (20, 40 mg/kg) were administered 10 min before reperfusion. Then after 4 h reperfusion, animals were sacrificed and immediately brain was removed, homogenized, centrifuged and supernatant was collected, various enzyme estimations were done and same procedure was followed in streptozotocin (STZ: 45 mg/kg; i.p.) induced diabetic rats.

RESULTS: Ischemia reperfusion (I/R) group showed significant increase in malondialdehyde (MDA), myeloperoxidase (MPO) and depletion in catalase (CAT) and superoxide dismutase (SOD) levels. Treatment with allopurinol and nimesulide significantly decreased the MDA and MPO levels whereas increased the SOD and CAT levels when compared I/R group in both non-diabetic and diabetic rats.

CONCLUSIONS: These findings suggest the cerebral injury due to over production of free radicals was inhibited by allopurinol and nimesulide that exert a neuroprotective effect probably by radical scavenging and antioxidant activities.

 

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