NF-κB-mediated inflammation correlates with calcium overload under arsenic trioxide-induced myocardial damage in Gallus gallus

Chemosphere. 2017 Oct:185:618-627. doi: 10.1016/j.chemosphere.2017.07.055. Epub 2017 Jul 14.

Abstract

Arsenic is a known environmental pollutant and highly hazardous toxin to human health. Due to the biological accumulation, arsenic produces a variety of cardiovascular diseases. However, the exact mechanism is still unclear. Here, our objective was to evaluate myocardial damage and determine the potential mechanism under arsenic exposure in chickens. Arsenic trioxide (As2O3) (1.25 mg/kg BW, corresponding 15 mg/kg feed) was administered as basal diet to male Hy-line chickens (one-day-old) for 4, 8 and 12 weeks. The results showed that As2O3-induced histological and ultrastructural damage in heart accompanied with significantly Ca2+ overload and increased the activities of myocardial enzymes. Moreover, As2O3 exposure significantly increased (P < 0.05) the mRNA levels of ITPR3, PMCA, TRPC1, TRPC3, STIM1, ORAI1 and pro-inflammatory genes, while the mRNA levels of ITPR1, ITPR2, RyR1, RyR3, SERCA, SLC8A1, CACNA1S and interleukin-10 were decreased (P < 0.05) by As2O3 exposure at 4, 8 and 12 weeks as compared with the corresponding control group. Western blot results showed that As2O3 exposure decreased the expression of SERCA and SLC8A1 protein, while the expression of TNF-α, NF-κB, iNOS and PMCA1 increased compared with the corresponding control group. Additionally, correlation analysis and protein-protein interaction prediction shown that NF-κB-mediated inflammatory response have a function correlation with calcium (Ca) regulation-related genes. In conclusion, this study indicated that As2O3-induced inflammatory response might dependent on Ca overload in myocardial damage of chickens. Our work has implications for the development of potential therapeutic approaches by resisting Ca overload for arsenic-induced myocardial damage.

Keywords: Arsenic; Calcium; Chickens; Heart; Inflammatory response.

MeSH terms

  • Animals
  • Arsenic / metabolism
  • Arsenic Trioxide
  • Arsenicals
  • Calcium, Dietary / metabolism*
  • Chickens / metabolism
  • Chickens / physiology*
  • Gene Expression Regulation
  • Heart / drug effects*
  • Heart / physiology
  • Inflammation
  • Inflammation Mediators
  • Interleukin-10 / metabolism
  • Male
  • Myocardium / metabolism
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II
  • Oxides / toxicity*
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Arsenicals
  • Calcium, Dietary
  • Inflammation Mediators
  • NF-kappa B
  • Oxides
  • RELA protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Arsenic
  • Arsenic Trioxide