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Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats

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Abstract

Purpose

High fructose (HFr) intake is known to cause insulin resistance syndrome (IRS), however its effect against acute coronary events remains elusive. The present study was undertaken to evaluate the effect of HFr (60%) diet on myocardial ischemia-reperfusion (MI-RP) injury and its modulation by atorvastatin treatment.

Methods

Wistar rats kept on HFr/chow feeding for 10 weeks, received atorvastatin (30 mg/kg, per oral) or vehicle for two additional weeks followed by MI-RP injury.

Results

MI-RP injury was significantly augmented in HFr fed rats, as evident by the increase in infarct size (IS, 65 ± 5% vs. 43 ± 7%) and activities of cardiac injury biomarkers [serum lactate dehydrogenase (LDH, 698 ± 57 vs. 444 ± 26 U/L), creatinine kinase (CK-MB, 584 ± 58 vs. 435 ± 28 U/L) and tissue myeloperoxidase (MPO, 235 ± 15 vs. 101 ± 11 μM/min/100 mg tissue)]. Insulin resistance (plasma glucose, 64 ± 5 vs. 100 ± 5 mg/dl; AUC 0−120 min, p < 0.05), MI-RP injury (IS 20 ± 5%, LDH 292 ± 28 U/L, CK-MB 257 ± 13 U/L, MPO 95 ± 5 μM/min/100 mg tissue) and triglyceride (TG) level were significantly reduced, while myocardial Akt, p-Akt, eNOS, p-eNOS and iNOS protein expression were significantly enhanced following atorvastatin treatment in comparison to HFr fed rats. Oxidative stress marker, malondialdehyde and circulating levels of inflammatory cytokines (CRP, IL-6, IFN-γ and TNF) were significantly reduced, while total nitrite content in the tissue and plasma was significantly augmented in atorvastatin treated rats. Atorvastatin also ameliorated endothelial dysfunction and significantly enhanced aortic Akt and eNOS protein expression.

Conclusion

Atorvastatin conferred significant protection against MI-RP injury and alleviated HFr induced IRS possibly by increasing NOS expression through Akt dependent pathway.

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Acknowledgements

This work was supported by Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research (CSIR), Government of India [NWP0034] and DBT-INDIGO project. We gratefully acknowledge the award of research fellowships by the Council of Scientific and Industrial Research (CSIR) and Indian Council of Medical Research (ICMR), India.

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  1. Pharmacology Division, CSIR-Central Drug Research Institute, 1. M.G. Marg, Lucknow, UP, 226001, India

    Prem Prakash, Vivek Khanna, Vishal Singh, Anupam Jyoti, Manish Jain, Ravi Shankar Keshari, Manoj Kumar Barthwal & Madhu Dikshit

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  1. Prem Prakash
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Prakash, P., Khanna, V., Singh, V. et al. Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats. Cardiovasc Drugs Ther 25, 285–297 (2011). https://doi.org/10.1007/s10557-011-6312-x

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