title: Atorvastatin protects against ischemia-reperfusion injury in fructose-induced insulin resistant rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Atorvastatin conferred significant protection against MI-RP injury and alleviated HFr induced IRS possibly by increasing NOS expression through Akt dependent pathway.
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, 1. M.G. Marg, Lucknow, UP, 226001, India.
authors.forename: Prem
authors.initials: P
authors.lastname: Prakash
authors.forename: Vivek
authors.initials: V
authors.lastname: Khanna
authors.forename: Vishal
authors.initials: V
authors.lastname: Singh
authors.forename: Anupam
authors.initials: A
authors.lastname: Jyoti
authors.forename: Manish
authors.initials: M
authors.lastname: Jain
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Keshari
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Barthwal
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D004730:Endothelium, Vascular / Q000187:drug effects; D005632:Fructose / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009573:Nitrites; D011758:Pyrroles; D005632:Fructose; D000069059:Atorvastatin; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt