title: Induction of inflammation, DNA damage and apoptosis in rat heart after oral exposure to zinc oxide nanoparticles and the cardioprotective role of α-lipoic acid and vitamin E.
abstract: Although zinc oxide nanoparticles (ZnO-NP) are being used on a wide scale in the world consumer market, their potential hazards on humans remain largely unknown. The present study was aimed at investigating the oral toxicity of ZnO-NP in 2 dose regimen (600 mg/kg and 1 g/kg body weight for 5 consecutive days) in rats. In addition, the protective role of either α-lipoic acid (Lipo) or vitamin E (Vit E) against this cardiotoxic effect of ZnO-NPs was assessed. Results revealed that, co-administration of Lipo (200 mg/Kg body weight) or Vit E (100 mg/Kg body weight) daily for 3 weeks to rats intoxicated with ZnO-NPs (in either of the 2 dose regimen) significantly ameliorated the cardiotoxic effect of these nanoparticles. As, both agents significantly reduced the increase in serum cardiac injury markers including troponin-T, creatine kinase-MB (CK-MB), and myoglobin. Additionally, Lipo and Vit E significantly decreased the increase in serum pro-inflammatory biomarkers level including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP). Moreover, either of the 2 used agents successfully alleviated the alteration in nitric oxide (NO) and vascular endothelial growth factor (VEGF) in ZnO-NPs in sera of intoxicated group. They also significantly reduced the increase in cardiac calcium concentration and the consequent oxidative deoxyribonucleic acid (DNA) damage, as well as the increase in cardiac caspase-3 activity of intoxicated rats. Conclusively, these results indicate that early treatment with either α-lipoic acid or vitamin E may offer protection against cardiac tissue injury induced by the deleterious toxic impacts of ZnO-NPs.
authors.affiliation: Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, KSA. nayiraabdelbaky@yahoo.com
authors.forename: N A A
authors.initials: NA
authors.lastname: Baky
authors.forename: L M
authors.initials: LM
authors.lastname: Faddah
authors.forename: N M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.forename: N M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.forename: A J
authors.initials: AJ
authors.lastname: Fatani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D006321:Heart / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced*; D053758:Nanoparticles / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D014810:Vitamin E; D008063:Thioctic Acid; D053148:Caspase 3; D015034:Zinc Oxide; D002118:Calcium