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

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.

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application

“…Prevention of dexamethasone-induced myotube atrophy via Akt/Foxo1 [154] Induction of p53 deficient SW480 cell apoptosis by ROS MAPK signaling [155] Role of microRNAs in the chemopreventive activity of SFN [156] Novel phosphonate analogs of SFN with in vitro and in vivo anti-cancer activity [157] Gastrointestinal protection against H. pylori and NSAID-Induced Oxidative Stress [158] Protection against sodium valproate-induced acute liver injury [159] Enhanced SFN cardioprotection against oxidative stress by 17β-Estradiol [159] Photoprotective Effects of SFN and Hispidulin [130] Improvement of neuronal mitochondrial function in brain tissue [160] Chemoprevention of oxidative stress-associated with oral carcinogenesis [161] Amelioration of bladder dysfunction via activation of Nrf2-ARE Pathway [162] Protection against aortic complications in diabetes [163] Anti-inflammatory effect against amyloid-β peptide via STAT-1 dephosphorylation and activation of Nrf2/HO-1 [164] Table 6. Sulphoraphane Applications in Cancer Models.…”

Effects of sulforaphane on brain mitochondria: mechanistic view and future directions

“…The authors also demonstrated that carnosic acid at a lower dose (1 mg/kg, i.p. Bi et al, 2017 SFN at 5 mg/kg administrated to rats that were exposed to iron during the nenonatal period Upregulated DNM1L/Drp1 in the hippocampus Lavich et al, 2015 SFN: sulforaphane; i.p. : intraperitoneal; tBOOH: tert-butyl hydroperoxide; 4-HNE: 4-hydroxynonenal; CO: carbon monoxide; OCR: oxygen consumption rate; ATP: adenosine triphosphate; MMP: mitochondrial membrane potential; ETC: electron transfer chain; Nrf2: nuclear factor erythroid 2-related factor 2; Trx-1: thioredoxin-1; NQO-1: nicotinamide adenine dinucleotide phosphate (NADPH):quinone oxidoreductase-1; DNM1L: dynamin-1-like protein, also called Drp1 administration) caused a similar protection (or even better results, as in the case of complex II-driven respiration) in the 4-HNE-challenged mitochondria.…”

“…Additional studies would be useful to understand exactly how SFN promotes mitochondrial protection in an experimental model of striatal excitotoxicity. Bi et al (2017) studied the effects of SFN in male Sprague Dawley rats submitted to carbon monoxide (CO) poisoning. The animals were treated with SFN at 10-40 mg/kg once a day by i.p.…”

The Glucosinolates, A Sulphur Glucoside Family of Mustard Phytochemicals With Diverse Biomedical Application

“…Suppression of NLRP3 inflammasome alleviating acute gouty inflammation [147] Modification of Histone H3, unpacking of chromatin, to prime defence [104] Nrf2-Inducers Counteract Neurodegeneration in Friedreich's Ataxia [148] Modulation of oxidative stress and inflammation in rats with toxic hepatitis [149] Modulation of oxidative damage in lead exposed rat hippocampus [150] Prevention of dexamethasone-induced myotube atrophy via Akt/Foxo1 [151] Induction of p53 deficient SW480 cell apoptosis by ROS MAPK signalling [152] Role of microRNAs in the chemo preventive activity of SFN [153] Up regulation of Nrf2 protection in doxorubicin-induced chronic heart failure [154] Increased Nrf2 expression protects alveolar epithelial cells against oxidative injury [155] Novel phosphonate analogs of SFN with in vitro and in vivo anticancer activity [156] Inhibition of PDGF-induced vascular SMC proliferation by targeting mTOR/p70S6kinase signalling independently of Nrf2 activation [157] Gastrointestinal protection against H. pylori and NSAID-Induced Oxidative Stress [158] Protection from cerebral ischemic/reperfusion injury via inhibition of NLRP3 inflammasome activation in rats [159] Protection against sodium valproate-induced acute liver injury [160] Enhanced SFN cardioprotection against oxidative stress by 17β-Estradiol [160] Photoprotective Effects of SFN and Hispidulin [106] Differential modulation of mitochondrial biogenesis/dynamics in normal and tumour cells [161] Nrf2 targeting by SFN: A potential therapy for cancer treatment [162,163] Improvement of neuronal mitochondrial function in brain tissue [164] Protection of pancreatic Acinar cell injury by modulating Nrf2-mediated oxidative stress and the NLRP3 inflammatory pathway [165] Improvement in chemotherapy efficacy targeting cancer stem cell-like properties [166] Protection against rotenone-induced neurotoxicity via mTOR, Nrf2, and autophagy [167] Chemoprevention of oxidative stress-associated with oral carcinogenesis [168] Amelioration of bladder dysfunction via activation of Nrf2-ARE Pathway [169] Broccoli sprout homogenate treatment for Sickle Cell Disease …”