摘要
目的研究9种光学活性黄皮酰胺类化合物体外对黄曲霉毒素B1(AFB1)引起大鼠肝细胞非程序性DNA合成(UDS)损伤和谷丙转氨酶(GPT)释放的保护作用有无差异。方法用胶原酶灌流法分离大鼠肝细胞。将分离的大鼠肝细胞与羟基脲(终浓度10 mmol.L-1)和所试化合物于37℃5%CO2培养1 h,再加入AFB1(终浓度0.1μmol.L-1)和[3H]TdR,测定UDS合成和GPT释放的量。结果所试9种光学活性黄皮酰胺类化合物在0.1 mol.L-1浓度时,右旋(+)黄皮酰胺、左旋(-)新黄皮酰胺、消旋(±)新黄皮酰胺、(-)表新黄皮酰胺和(±)表新黄皮酰胺对AFB1引起的大鼠肝细胞UDS损伤有显著的阻抑作用;而(-)黄皮酰胺、(+)新黄皮酰胺和(±)新黄皮酰胺、(-)表新黄皮酰胺和(±)表新黄皮酰胺则能显著抑制AFB1引起的大鼠肝细胞GPT的释放。(±)黄皮酰胺和右旋表新黄皮酰胺二者则对UDS损伤和GPT释放均无影响。结论黄皮酰胺类化合物对上述的AFB1引起大鼠肝细胞非程序性UDS合成的损伤和GPT释放的不同作用与其立体结构的不同有关系,5S6R构型有利于保护AFB1引起的大鼠肝细胞UDS损伤,而5R6S构型则利于保护AFB1引起的大鼠肝细胞GPT的释放。
AIM To study if there are different effects of 9 enantiomers of clausenamides on aflatoxin B1 （AFB1 ）-induced unscheduled DNA synthesis （UDS） injury and glutamic-pyruvic transferase （GPT） release of isolated rat hepatocytes in vitro. METHODS The isolated rat hepatocytes were cultured with 10 mmol·L^-1 hydroxyurea and 0. 1 mmol·L^-1 of each tested clausenamide, respectively, at 37℃ in 5% CO2-95% O2 incubator for 1 h, and then cultured with 0. 1 μmmol·L^-1 AFB1 and [ ^3H ] TdR for 4 h. UDS injury of the hepatocytes and the released GPT in the medium were determined, respectively. RESULTS Among the nine clausenamides, （ ＋ ） clausenamide, （ - ） neoclausenamide, （ ± ） neoclausenamide, （ - ） epineoclausenamide and （ ± ）epineoclausenamide significantly protected against AFB1-induced UDS injury; while （ - ） clausenamide, （ ＋ ） neoclausenamide, （ ± ） neoclausenamide, （ - ） epineoclausenamide and （ ± ） epineoclausenamide markedly inhibited GPT release of rat hepatocytesinduced by AFB, （ ± ） clausenamide and （ ＋ ） epineoclausenamide showed no effect on AFB1-induced both UDS injury and GPT release of the hepatocytes. CONCLUSION The different effect of clausenamides on AFB1-induced UDS injury and GPT release is related to the variations of configuration of their structures, the clausenamide with the 5S6R configuration is beneficial to protection against AFB1 induced UDS injury, while 5R6S configuration of clausenamide is effective for inhibiting GPT release induced by AFB1 in rat hepatocytes.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2006年第5期393-398,共6页
Chinese Journal of Pharmacology and Toxicology
