亚硝酸钠(SN),一种流行的食品防腐剂,已知暴露后会沉淀肝毒性。本研究阐明了玉米寡肽(COP)和维生素E(VE)对SN诱导的犬肝细胞肝损伤的保护作用。犬肝细胞进行SN诱导肝毒性,然后用COP和VE治疗。评估包括细胞活力测定,氧化应激标志物,凋亡,和炎性细胞因子。此外,进行转录组和代谢组学分析以描绘潜在的分子机制。结果表明,COP和VE显著改善了SN诱导的细胞毒性,氧化应激,和凋亡。细胞活力恢复证明了这一点,增强抗氧化酶活性,减少细胞质酶渗漏,丙二醛和炎性细胞因子水平降低,COP表现出优越的疗效。RNA测序显示COP处理抑制了SN激活的氨酰-tRNA生物合成途径和TGF-β/NF-κB信号通路,从而减轻氨基酸消耗,凋亡,和炎症。此外,COP处理上调与蛋白质折叠相关的基因,胆汁酸合成,DNA修复代谢组学分析证实了这些结果,表明COP恢复了氨基酸水平并增强了胆汁酸代谢,减轻SN诱导的代谢破坏。这些发现为COP的保护机制提供了重要的见解,强调了其在治疗肝损伤中的未来应用。
Sodium nitrite (SN), a prevalent food preservative, is known to precipitate hepatotoxicity upon exposure. This study elucidates the hepatoprotective effects of corn oligopeptide (COP) and vitamin E (VE) against SN-induced hepatic injury in canine hepatocytes. Canine liver cells were subjected to SN to induce hepatotoxicity, followed by treatment with COP and VE. Evaluations included assays for cell viability, oxidative stress markers, apoptosis, and inflammatory cytokines. Additionally, transcriptomic and metabolomic analyses were performed to delineate the underlying molecular mechanisms. The findings demonstrated that COP and VE significantly ameliorated SN-induced cytotoxicity, oxidative stress, and apoptosis. It was evidenced by restored cell viability, enhanced antioxidant enzyme activity, reduced cytoplasmic enzyme leakage, and decreased levels of malondialdehyde and inflammatory cytokines, with COP showing superior efficacy. The RNA sequencing revealed that COP treatment suppressed the SN-activated aminoacyl-tRNA biosynthesis pathway and TGF-β/NF-κB signaling pathways, thereby mitigating amino acid depletion, apoptosis, and inflammation. Moreover, COP treatment upregulated genes associated with protein folding, bile acid synthesis, and DNA repair. Metabolomic analysis corroborated these results, showing that COP restored amino acid levels and enhanced bile acid metabolism, alleviating SN-induced metabolic disruptions. These findings offered significant insights into the protective mechanisms of COP underscoring its prospective application in treating liver injuries.