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.

Bio‐effect of nanoparticles in the cardiovascular system

“…Moreover, the ZnO NPs could synergistically enhance the TNF‐α‐induced, NF‐κB signaling‐dependent ICAM‐1 expression . Following ZnO NP exposure, increased the serum levels of TnT, CK‐MB and myoglobin, markers of cardiac injury, increased serum levels of pro‐inflammatory factors, including TNF‐α, IL‐6, and CRP, alterations in the NO and VEGF concentrations, DNA damage, increased cardiac calcium concentrations and increased cardiac caspase‐3 activity were observed in the rat heart …”

“…The NP‐induced inflammatory response is a common phenomenon in the CV system . The hypothesis that inhaled particles exert indirect effects on the CV system by transporting inflammatory mediators from the lung to the systemic circulation has been investigated .…”

Endoplasmic reticulum stress and oxidative stress are involved in ZnO nanoparticle-induced hepatotoxicity

“…Previous studies have shown that Nano-ZnO mainly accumulate in the liver, pancreas, kidney, heart, spleen and lungs after they entered the body through skin, respiratory tract and gastrointestinal tract exposures (Baek et al, 2012; Baky et al, 2013; Cho et al, 2011; Cho et al, 2013; Chuang et al, 2014; Pasupuleti et al, 2012; Seok et al, 2013; Sharma et al, 2012a; Sharma et al, 2012b; Wang et al, 2006). In this study, we mainly focused on the hepatotoxic effects of Nano-ZnO and the potential mechanisms.…”

Toxicity assessment of nanoparticles in various systems and organs

“…As for cardiac injury, serum markers, like troponin-T, creatine kinase-MB, and myoglobin, should be analyzed [80]. Cardiac calcium concentration associated with contraction function and DNA damage also needs to be determined.…”