Ray S D, Sorge C L, Tavacoli A, Raucy J L, Corcoran G B
Toxicology Program, College of Pharmacy, University of New Mexico, Albuquerque 87131.
Adv Exp Med Biol. 1991;283:699-705. doi: 10.1007/978-1-4684-5877-0_90.
Hepatotoxic doses of acetaminophen cause early impairment of Ca2+ homeostasis. In this in vivo study, 600 mg/kg acetaminophen caused total nuclear Ca2+ and % fragmented DNA to rise in parallel from 2-6 hr, followed by large later increases mirroring frank liver injury. Agarose gel electrophoresis revealed substantial loss of large genomic DNA from 2 hours onward, with accumulation of DNA fragments in a ladder-like pattern resembling apoptosis. Extensive late cleavage of DNA probably resulted from cell death, whereas degradative loss of large genomic DNA at 2 hours arose at an early enough point to contribute to acetaminophen-induced liver necrosis in mice.
对乙酰氨基酚的肝毒性剂量会导致早期钙离子稳态受损。在这项体内研究中，600毫克/千克的对乙酰氨基酚导致细胞核内总钙离子含量和DNA片段化百分比在2至6小时内平行上升，随后大幅增加，这反映了明显的肝损伤。琼脂糖凝胶电泳显示，从2小时起，大量基因组DNA显著丢失，DNA片段呈梯状积累，类似于细胞凋亡。DNA的广泛后期切割可能是细胞死亡所致，而2小时时大片段基因组DNA的降解性丢失发生得足够早，导致了对乙酰氨基酚诱导的小鼠肝坏死。
