Sulphoraphane Improves Neuronal Mitochondrial Function in Brain Tissue in Acute Carbon Monoxide Poisoning Rats

Basic Clin Pharmacol Toxicol. 2017 Jun;120(6):541-549. doi: 10.1111/bcpt.12728. Epub 2017 Mar 30.

Abstract

Carbon monoxide (CO) poisoning is one of the leading causes of toxicity-related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of this study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulphoraphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO. We found that CO poisoning could induce advanced cognitive dysfunction, while the mitochondrial ultrastructure of neurons in rats of the CO poisoning group was seriously damaged and mitochondrial membrane potential (ΔΨm) was accordingly reduced by transmission electron microscopy (TEM) and JC-1 fluorescent probe assay. CO poisoning could also increase the expressions of both nuclear factor erythroid 2-related factor 2 (Nrf-2) and thioredoxin-1 (Trx-1) proteins and their mRNA in brain tissue with immunohistochemistry and quantitative PCR (qPCR) techniques. Early administration of either middle-dose or high-dose SFP could efficiently improve mitochondrial structure and function and enhance the antioxidative stress ability, thus exerting a positive effect against brain damage induced by acute CO poisoning.

MeSH terms

  • Acute Disease
  • Animals
  • Brain / drug effects*
  • Brain / ultrastructure
  • Carbon Monoxide Poisoning / drug therapy*
  • Carbon Monoxide Poisoning / metabolism
  • Isothiocyanates / pharmacology*
  • Isothiocyanates / therapeutic use
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Mitochondria / ultrastructure
  • NF-E2-Related Factor 2 / physiology
  • Neurons / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Sulfoxides
  • Thioredoxins / physiology

Substances

  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Reactive Oxygen Species
  • Sulfoxides
  • Txn1 protein, rat
  • Thioredoxins
  • sulforaphane