Muhieddine Dina, Moughnié Mohamad, Abdel-Razzak Ziad
Laboratory of Experimental and Clinical Pharmacology, Faculty of Sciences, Rafic Hariri Campus, Lebanese University, Beirut, Lebanon.
Interdiscip Toxicol. 2019 Sep;12(1):41-44. doi: 10.2478/intox-2019-0006. Epub 2020 Feb 20.
Chlorpromazine (CPZ) is still a commonly prescribed antipsychotic which causes poorly understood idiosyncratic toxicity such as cholestasis, phospholipidosis and steatosis. CPZ has diverse cellular targets and exerts various toxicity mechanisms whose exploration is necessary to understand CPZ side effects. We report here that CPZ causes a decrease of total lipid content in at the same dose range as that used on mammalian cells. The observed lipid decrease was obvious after 4 and 9 hours of treatment, and disappeared after 24 hours due to cells adaptation to the chemical stress. The inhibitory effect of CPZ was antagonized by the antioxidant N-acetyl L-cysteine and is likely caused by the parent compound. The obtained results demonstrate that yeast model is valid to investigate the involved CPZ toxicity mechanisms, particularly in terms of lipids alteration. This would contribute to understand CPZ side effects in simple model and reduce experimentation on animals.
氯丙嗪(CPZ)仍是一种常用的抗精神病药物,它会引发如胆汁淤积、磷脂沉积症和脂肪变性等了解甚少的特异质性毒性。CPZ具有多种细胞靶点,并发挥着各种毒性机制,对其进行探索对于理解CPZ的副作用是必要的。我们在此报告,在与用于哺乳动物细胞相同的剂量范围内,CPZ会导致酵母细胞中总脂质含量下降。在处理4小时和9小时后,观察到的脂质减少很明显,而在24小时后由于细胞适应化学应激而消失。CPZ的抑制作用被抗氧化剂N-乙酰半胱氨酸拮抗,并且可能是由母体化合物引起的。所获得的结果表明,酵母模型对于研究CPZ相关的毒性机制是有效的,特别是在脂质改变方面。这将有助于在简单模型中理解CPZ的副作用,并减少动物实验。