Exp Clin Cardiol. 2008;13(2):66-70.
Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats.
Experimental and clinical cardiology
Akula Annapurna, Siva Reddy Challa, Gomedhikam J Prakash, Routhu Kasi Viswanath
Affiliations
Affiliations
- Department of Pharmacology, University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam - 530 003, Andhra Pradesh, India.
PMID: 19343118
PMCID: PMC2586398
Abstract
BACKGROUND: Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state.
OBJECTIVES: To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats.
METHODS: Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically.
RESULTS: Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats.
CONCLUSIONS: The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.
Keywords: Cardioprotection; Diabetes; Polyol pathway; Reperfusion injury; Sulindac
References
- Diabetes Res Clin Pract. 1990 Aug-Sep;10(1):91-7 - PubMed
- Neurology. 1990 Sep;40(9):1446-9 - PubMed
- J Lab Clin Med. 1987 Jul;110(1):13-30 - PubMed
- J Intern Med. 1994 Sep;236(3):291-7 - PubMed
- Anal Biochem. 1979 Jun;95(2):351-8 - PubMed
- N Engl J Med. 1987 Mar 5;316(10):599-606 - PubMed
- Cardiovasc Res. 1987 Oct;21(10):755-60 - PubMed
- Am Heart J. 1981 May;101(5):593-600 - PubMed
- Free Radic Biol Med. 2003 Nov 1;35(9):1008-17 - PubMed
- Can J Neurol Sci. 1992 Nov;19(4):433-41 - PubMed
- Diabetes. 1995 Feb;44(2):234-42 - PubMed
- J Am Coll Cardiol. 1995 Feb;25(2):370-7 - PubMed
- FASEB J. 2003 Dec;17(15):2331-3 - PubMed
- Biochim Biophys Acta. 1985 Sep 6;841(3):247-53 - PubMed
- Am Heart J. 1990 Mar;119(3 Pt 1):530-7 - PubMed
- Cardiovasc Res. 1997 Apr;34(1):113-20 - PubMed
- Am J Physiol. 1998 Jul;275(1):H195-203 - PubMed
- Diabetes. 1997 Feb;46(2):292-300 - PubMed
- Biochem Med. 1976 Apr;15(2):212-6 - PubMed
- J Cardiovasc Pharmacol. 1988 Sep;12(3):338-44 - PubMed
- J Clin Invest. 1995 Aug;96(2):733-40 - PubMed
- Diabetes. 1993 Jun;42(6):801-13 - PubMed
- Vascul Pharmacol. 2005 Aug;43(2):91-100 - PubMed
- J Biol Chem. 1951 Nov;193(1):265-75 - PubMed
- Nature. 1993 Apr 29;362(6423):801-9 - PubMed
- FASEB J. 2004 Aug;18(11):1192-9 - PubMed
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