Nakagawa Y, Tayama S
Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Arch Toxicol. 1995;69(3):204-8. doi: 10.1007/s002040050159.
The cytotoxic effects of propyl gallate (PG), its related gallates and gallic acid have been studied in freshly isolated rat hepatocytes. Addition of PG (0.5-2.0 mM) to hepatocyte suspension elicited concentration-dependent cell death accompanied by losses of intracellular ATP, adenine nucleotide pools, glutathione (GSH) and protein thiols. The rapid loss of intracellular ATP preceded the onset of cell death caused by PG. In the comparative toxic effects of PG and related gallates at concentration of 1 mM, octyl gallate (OG), dodecyl gallate (DG) and butyl gallate (BG) elicited an abrupt depletion of ATP, followed by an acute cell death. These gallates were more toxic than PG; the toxic effects of PG were similar to those of methyl gallate (MG) and ethyl gallate (EG). In mitochondria isolated from rat liver, PG caused a concentration-dependent increase in the rate of state 4 oxygen consumption, indicating an uncoupling effect. The rate of state 3 oxygen consumption was inhibited by OG and DG. According to the respiratory control index, the order of impairment potency to mitochondria was OG > BG, DG > PG > EG, MG > gallic acid. These results indicate that PG and related gallates are toxic to hepatocytes and that the acute cytotoxicity may be due to mitochondrial dysfunction.
没食子酸丙酯（PG）、其相关没食子酸盐和没食子酸对新鲜分离的大鼠肝细胞的细胞毒性作用已被研究。向肝细胞悬液中添加PG（0.5 - 2.0 mM）会引发浓度依赖性细胞死亡，并伴有细胞内ATP、腺嘌呤核苷酸池、谷胱甘肽（GSH）和蛋白质巯基的损失。细胞内ATP的快速损失先于PG引起的细胞死亡。在1 mM浓度下PG和相关没食子酸盐的比较毒性作用中，没食子酸辛酯（OG）、没食子酸十二酯（DG）和没食子酸丁酯（BG）会导致ATP突然耗尽，随后是急性细胞死亡。这些没食子酸盐比PG毒性更大；PG的毒性作用与没食子酸甲酯（MG）和没食子酸乙酯（EG）相似。在从大鼠肝脏分离的线粒体中，PG导致状态4氧消耗速率呈浓度依赖性增加，表明存在解偶联效应。状态3氧消耗速率受到OG和DG的抑制。根据呼吸控制指数，对线粒体损伤能力的顺序为OG > BG，DG > PG > EG，MG > 没食子酸。这些结果表明PG和相关没食子酸盐对肝细胞有毒，并且急性细胞毒性可能是由于线粒体功能障碍。
