Green Synthesized Zinc Oxide Nanoparticles Attenuate Acrylamide-Induced Cardiac Injury via Controlling Endoplasmic Reticulum Stress-Associated Apoptosis Through ATF3/CHOP/BCL2 Signaling in Rats

Biol Trace Elem Res. 2024 Jun;202(6):2657-2671. doi: 10.1007/s12011-023-03855-1. Epub 2023 Sep 27.

Abstract

Due to their distinctive properties, several eco-friendly metal oxide nanoparticles were assessed for their possible cardioprotective properties. Acrylamide (ACD), a pervasive chemical in food and the environment, has been linked to cardiac toxicity. Therefore, this study examined the probable protective effect of green synthesized zinc oxide nanoparticles (GS-ZNPs) against ACD-oral exposure-induced cardiac damage in rats. For 60 days, 40 male Sprague-Dawley rats were separated into four sets that orally administered distilled water, 10-mg GS-ZNP/kg b.w., 20-mg ACD/kg b.w., or GS-ZNP + ACD. Then, cardiac damage indicators comprising CPK, CK-MB, cTn, and LDH were assessed. Besides, cardiac tissues' architecture, oxidative stress indicators, and Zn content were evaluated. The mRNA expression of the ERS-related genes, including ATF3, ATF4, ATF6, XBP-1, CHOP, JNKs, and BiP, were determined. Moreover, ERS-dependent anti-apoptotic (BCL-2) and apoptotic (Caspase-3 and BAX) genes mRNA expression were analyzed. The results showed that GS-ZNP significantly alleviated the increased ACD-induced serum cardiac damage indicators, MDA tissue content, and histopathological changes. Furthermore, the ACD-induced reduction of antioxidants and Zn heart contents were significantly reestablished by GS-ZNP. Furthermore, the ACD-induced upregulation of the ERS-encoding genes and apoptotic genes was reversed by GS-ZNP. Besides, the ACD-induced BCL-2 downregulation was counteracted by GS-ZNP. Overall, GS-ZNP could be a biologically potent compound to alleviate ACD's cardiotoxic effects, possibly by controlling the ERS and apoptosis-related genes and antioxidant activity.

Keywords: Acrylamide; Apoptosis; Endoplasmic reticulum stress; Heart; Zinc oxide nanoparticles; mRNA.

MeSH terms

  • Acrylamide* / toxicity
  • Activating Transcription Factor 3 / metabolism
  • Animals
  • Apoptosis* / drug effects
  • Endoplasmic Reticulum Stress* / drug effects
  • Green Chemistry Technology
  • Heart Injuries / chemically induced
  • Heart Injuries / drug therapy
  • Heart Injuries / metabolism
  • Heart Injuries / pathology
  • Heart Injuries / prevention & control
  • Male
  • Metal Nanoparticles / chemistry
  • Nanoparticles / chemistry
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-2* / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • Signal Transduction* / drug effects
  • Transcription Factor CHOP* / metabolism
  • Zinc Oxide* / chemistry
  • Zinc Oxide* / pharmacology

Substances

  • Zinc Oxide
  • Acrylamide
  • Proto-Oncogene Proteins c-bcl-2
  • Bcl2 protein, rat
  • Transcription Factor CHOP
  • Activating Transcription Factor 3
  • Ddit3 protein, rat