title: Protective effects of arjunolic acid against cardiac toxicity induced by oral sodium nitrite: effects on cytokine balance and apoptosis.
abstract: OBJECTIVE
  Sodium nitrite, a preservative used in meat products, helps in the production of free radicals, leading to increased lipid peroxidation, which plays a vital role in posing toxic effects in different body organs. On the other hand, arjunolic acid possesses antioxidant properties and plays protective roles against chemically induced organ pathophysiology. We investigated the effect of sodium nitrite on cardiac tissue in rats on the inflammatory cytokine balance and the type of induced apoptosis, and we analyzed the protective role of arjunolic acid.
  
  
  METHODS
  Sixty adult male Sprague-Dawley rats were injected with 80mg/kg sodium nitrite in the presence/absence of arjunolic acid (100 and 200mg/kg). Cardiac pro-inflammatory cytokines (TNF-α and IL-1β), c-reactive protein (CRP) and anti-inflammatory cytokines (IL-4 and IL-10) were measured by ELISA. Cardiac mitochondrial activity (cytochrome-C-oxidase), JNK activation and apoptosis (caspase-3, caspase-8 and caspase-9) were assessed.
  
  
  RESULTS
  Sodium nitrite resulted in increased TNF-α (1.6-fold), IL-1β (3.7-fold) and CRP (2.4-fold) levels accompanied by 52%, 59% and 40% reductions in IL-10, IL-4 and cytochrome-C-oxidase, respectively, as well as enhanced JNK, caspase-3, caspase-8 and caspase-9 activities. Arjunolic acid markedly ameliorated these effects.
  
  
  CONCLUSIONS
  Arjunolic acid attenuated sodium nitrite-induced cardiac damage in rats and restored the normal balance between pro- and anti-inflammatory cytokines. Moreover, arjunolic acid protected cardiac tissues from both extrinsic and intrinsic cell death pathways.
authors: Dept. of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt; Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia. Electronic address: mhgayyar@yahoo.com.
authors: Mohammed M H
authors: MM
authors: Al-Gayyar
authors: Dept. of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk 71471, Saudi Arabia.
authors: Abdullah
authors: A
authors: Al Youssef
authors: Dept. of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors: Iman O
authors: IO
authors: Sherif
authors: Dept. of Pharmaceutics, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors: Mohamed E E
authors: ME
authors: Shams
authors: Dept. of Pharmacognosy, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors: Ahmed
authors: A
authors: Abbas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D016753:Interleukin-10 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; C061640:arjunolic acid; D002097:C-Reactive Protein; D003576:Electron Transport Complex IV; D012977:Sodium Nitrite
keywords: Caspase-3/8/9; Cytochrome C oxidase; Interleukin (IL)-1β/4/10; JNK MAPK; Tumor necrosis factor (TNF)-α