Xue, Liming; Xu, Jiale; Feng, Chao; Zhou, Zhijun; Jin, Yu’e; Lu, Dasheng; Wang, Guoquan published the artcile< Flurochloridone induces responses of free radical reactions and energy metabolism disorders to BRL-3A cell>, Application In Synthesis of 112-63-0, the main research area is free radical reaction energy metabolism disorder BRL 3A flurochloridone; AKT/GSK-3β; Energy metabolism dysfunction; Flurochloridone; Glucose isotopic tracing flux technology; Hepatotoxicity.
Flurochloridone (FLC), a wildly used herbicide, could induce hepatotoxicity after long-term exposure to male rat, in addition to its reactive oxygen species (ROS)-dependent reproductive toxicity. The hepatotoxicity effect and mechanism was investigeted using 1, 10 and 100μmol L-1 FLC treated BRL-3A liver cell in this study. The function of mitochondrial respiration, glycolysis rate and real time ATP production rate are determined by seahorse XF analyzer, and the bio-transformers of FLC, intermediates of TCA cycle and glycolysis, and related amino acids are determined and identified by [U-13C] Glucose metabolic flux technol. based on UPLC-HRMS. The mRNA expression of cytochrome P450s and the key regulatory enzymes of glucose metabolism and γ- glutamyl cycle pathway. The protein expressions of protein kinase B (AKT) and glycogen synthase kinase-3 beta (GSK-3β) were determined The results show dechlorination and glutathione (GSH) conjugate products of FLC are predominant bio-transformmers after 24 h treatment in BRL-3A cell. FLC could enhance glycolysis function and inhibit mitochondrial aerobic respiratory, which is accompanied by the decreased total ATP level and ATP produced rate. Increased glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate levels, and elevated level of GSH and its precursor 5-glutamate-cysteine (γ-Glu-Cys) are observed in FLC treated cells, which indicates that energy metabolism dysfunction and GSH accumulation could be potentially mediated by activating γ- Glutamyl cycle pathway. Conclusively, FLC induced hepatotoxicity could be potentially related to some free radical reactions, including inhibiting mitochondrial function, glucose metabolism via glycolysis, regulating γ- glutamyl cycle pathway to promote reactive oxygen species (ROS) level, and then induced cell apoptosis by inhibiting AKT/GSK-3β signal.
Ecotoxicology and Environmental Safety published new progress about Animal cell line (BRL-3A). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Application In Synthesis of 112-63-0.
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