T-2 toxin induces cardiac fibrosis by causing metabolic disorders and up-regulating Sirt3/FoxO3α/MnSOD signaling pathway-mediated oxidative stress.
Lichun QiaoXue LinHaobiao LiuRongqi XiangJingming ZhanFeidan DengMiaoye BaoHuifang HeXinyue WenHuan DengXining WangYujie HeZhihao YangJing HanPublished in: Journal of environmental sciences (China) (2024)
T-2 toxin, an omnipresent environmental contaminant, poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity. This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin. Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0, 10, and 100 nanograms per gram body weight per day (ng/(g·day)), respectively. Morphological, pathological, and ultrastructural alterations in cardiac tissue were meticulously examined. Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites. The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected. The results showed that exposure to T-2 toxin elicited myocardial tissue disorders, interstitial hemorrhage, capillary dilation, and fibrotic damage. Mitochondria were markedly impaired, including swelling, fusion, matrix degradation, and membrane damage. Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiac metabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway. T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress. In conclusion, the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway. This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
Keyphrases
- oxidative stress
- signaling pathway
- escherichia coli
- pi k akt
- induced apoptosis
- left ventricular
- diabetic rats
- ischemia reperfusion injury
- epithelial mesenchymal transition
- dna damage
- body weight
- transcription factor
- healthcare
- cell proliferation
- systemic sclerosis
- amino acid
- cell death
- poor prognosis
- mental health
- heat shock
- long non coding rna
- drug delivery
- cancer therapy
- endothelial cells
- heat stress