联苯双酯对他克林引起的肝损伤的保护作用

目的　观察联苯双酯(DDB)对他克林(THA)诱发小鼠肝损伤的保护作用。方法　小鼠一次poTHA(56mg·kg^-1) ,观察12h内动物血清ALT ,肝脏MDA和动物体温的改变;分光光度法测定小鼠脑乙酰胆碱酯酶活性;酶动力法测定小鼠肝微粒体7-乙氧基香豆素脱乙基酶和UDP葡糖醛酸转移酶(UDPGT)的活性;荧光法测定线粒体膜电位的改变。结果　DDB 200 mg·kg^-1 可明显保护THA引起的小鼠体温下降、血清ALT和肝脏MDA的升高。DDB(100 μmol·L^-1 )可减轻THA造成的大鼠线粒体膜电位降低。DDB还可提高小鼠肝微粒体7-乙氧基香豆素脱乙基酶的活性,但对UDPGT无影响。结论　DDB似通过降低肝脏脂质过氧化反应、提高线粒体膜稳定性、调节THA代谢酶活性发挥其肝保护作用

EFFECT OF DIMETHYL DIPHENYL BICARBOXYLATE (DDB) ON 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE-INDUCED HEPATOTOXICITY IN MICE

AIM: To establish an acute model of THA-induced hepatotoxicity in mice, and observe the effects of DDB on THA-induced liver damage. METHODS: After a single oral dose of THA (56 mg.kg-1), body temperatures, liver MDA content and serum ALT were measured within 12 h. The activities of mice brain acetylcholinesterase, liver microsomal 7-ethoxyresorufin deethylase, uridine-5'-diphosphoglucuronic transferase, and mitochondria potential change were also observed. RESULTS: The alteration of mice body temperature, and the elevation of serum ALT, liver MDA content, and mitochondria potential induced by THA were significantly inhibited by DDB pretreatment. The microsomal 7-ethoxyresorufin deethylase activity was induced by DDB too. On the other hand, The inhibiting effects of THA on mice hippocampus and cortex acetylcholinesterase in vitro and in vivo were not influenced by DDB treatment. CONCLUSION: The toxic effect of THA on mice liver was significantly reduced by DDB. These results demonstrate that the protective action of DDB may attribute to its regulation on enzymes involved in THA metabolism, and its protective effect against mitochondria injury caused by THA. Therefore, DDB may be a potential liverprotector against THA-induced hepatotoxicity during dementia therapy.