US EPA

3224103 

Journal Article 

Sulfur dioxide contributes to the cardiac and mitochondrial dysfunction in rats 

Qin, G; Wu, M; Wang, J; Xu, Z; Xia, J; Sang, N 

2016 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

151 

2 

334-346 

English 

26980303 

WOS:000377431600012 

http://toxsci.oxfordjournals.org/content/151/2/334.long
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Epidemiological studies have demonstrated an association between sulfur dioxide (SO2) and an increase of morbidity and mortality of cardiovascular diseases, such as ischemic heart disease, heart failure, and arrhythmia. Mitochondrion is the most sensitive organelle in myocardium of animals exposed to SO2 Here we study the molecular characterization of mitochondrial dysfunction in cardiac muscles of rat after SO2exposure. We found that the cytochrome c oxidase (COX) activity, mitochondrial membrane potential (ΔΨm), ATP contents, mitochondrial DNA (mtDNA) contents, and mRNA expression of complexes IV and V subunits encoded by mtDNA were decreased after NaHSO3treatmentin vitroor SO2inhalationin vivo The mitochondrial dysfunctions were accompanied by depressions of co-activator of peroxisome proliferator activated receptor gamma (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM) mRNA and protein. We observed swollen mitochondria and lower amounts of cristae in hearts of rats after 3.5 mg/m(3)SO2inhalation for 30 days. Interestingly, NaHSO3induced mitochondrial dysfunctions marked by ΔΨm and ATP reduction could be inhibited by an antioxidant N-acetyl-L-cysteine (NALC), accompanied by the restoration of transcriptional factors expressions. The cardiac mitochondrial dysfunctions could also be alleviated by overexpression of TFAM. SO2induced abnormal left ventricular function was restored by NALC in vivo Our findings demonstrate that SO2induces cardiac and mitochondrial dysfunction. And inhibition of reactive oxygen species and enhancing the transcriptional network controlling mitochondrial biogenesis can mitigate the SO2-induced mitochondrial dysfunction. 

sulfur dioxide; mitochondria; reactive oxygen species; TFAM; cardiac muscles