Department of Toxicology, Ch. Charan Singh University, Meerut, 250 004, India.
Appl Biochem Biotechnol. 2023 Nov;195(11):6856-6866. doi: 10.1007/s12010-023-04401-4. Epub 2023 Mar 22.
Biochemical and/or molecular mechanisms of arsenic or fluoride toxicity in experimental animals have been widely investigated in the recent past. However, their combined effects on target cells/organelle are poorly understood. The present study was executed to delineate their combined effects on mitochondrial function in the liver of rat. Female Wistar rats (140 ± 20 g) were force fed individually or in combination with sodium arsenate (4 mg/kg body weight) and sodium fluoride (4 mg/kg body weight) for 90 days. Thereafter, established markers of mitochondrial function viz. mitochondrial lipid peroxidation, oxidative phosphorylation, ATPase, succinic dehydrogenase, and caspase-3 activity were determined. Cytochrome C release and oxidative DNA damage were also estimated in the liver of respective groups of rats. The study showed significant differences in these results amongst the three groups. Observations on parameters viz. LPO, cytochrome-C, caspase-3, and 8-OHdG suggested an antagonistic relationship between these two elements. Results on ATPase, SDH, and ADP:O ratio indicated synergism. It is concluded that As + F in combination may express differential effects on signalling pathways and proapoptotic/antiapoptotic proteins/genes that contribute to liver cell death. Interaction of As and F with mitochondria.
在过去的一段时间里，人们广泛研究了砷或氟化物在实验动物中的毒性的生化和/或分子机制。然而，它们对靶细胞/细胞器的联合作用还了解甚少。本研究旨在阐明它们在大鼠肝脏线粒体功能中的联合作用。雌性 Wistar 大鼠（140±20g）单独或联合给予亚砷酸钠（4mg/kg 体重）和氟化钠（4mg/kg 体重）90 天。然后，测定线粒体功能的既定标志物，即线粒体脂质过氧化、氧化磷酸化、ATP 酶、琥珀酸脱氢酶和 caspase-3 活性。还测定了各组大鼠肝脏中的细胞色素 C 释放和氧化 DNA 损伤。研究结果表明，这三个组之间存在这些结果的显著差异。关于 LPO、细胞色素 C、caspase-3 和 8-OHdG 等参数的观察结果表明，这两种元素之间存在拮抗关系。关于 ATP 酶、SDH 和 ADP：O 比的结果表明存在协同作用。结论是，砷和氟的联合作用可能对导致肝细胞死亡的信号通路和促凋亡/抗凋亡蛋白/基因产生不同的影响。砷和氟与线粒体的相互作用。
