Kondo Kazunari, Watanabe Asako, Akiyama Hiroshi, Maitani Tamio
Division of Biosignaling, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
Food Chem Toxicol. 2008 Mar;46(3):854-62. doi: 10.1016/j.fct.2007.10.022. Epub 2007 Dec 3.
The mushroom hydrazine agaritine was measured in mouse plasma and urine using LC/MS/MS, which is highly specific. Agaritine concentration peaked 20 min after oral administration to mice (4.0 and 40 mg/kg). The concentration gradually decreased and returned to the basal level in 100 min. The maximum concentration, the time to the maximum concentration, and the half life were 0.37 microg/ml plasma, 0.33 h, and 0.71 h, respectively after administration of agaritine at 40 mg/kg body weight. One agaritine metabolite was found in the plasma and the urine from agaritine-administered mice. The structure of metabolites of agaritine by gamma-GT was next investigated using LC/MS. HMPH proved to be generated from agaritine. The oxidative stress marker 8-OHdG was detected in agaritine-administered mouse urine. After administration, the 8-OHdG level immediately tripled, and then decreased to the control level over 48 h. Its level then elevated again and remained high for 11 days. These results suggest that agaritine quickly metabolizes and disappears in the plasma, whereas DNA damage lasts for a long time after a single administration of agaritine to mice.
采用高特异性的液相色谱-串联质谱法（LC/MS/MS）测定小鼠血浆和尿液中的蘑菇肼类毒素伞菌氨酸。给小鼠口服伞菌氨酸（4.0和40 mg/kg）后，其浓度在20分钟时达到峰值。随后浓度逐渐下降，并在100分钟时恢复至基础水平。以40 mg/kg体重给予伞菌氨酸后，血浆中的最大浓度、达到最大浓度的时间和半衰期分别为0.37 μg/ml、0.33小时和0.71小时。在给予伞菌氨酸的小鼠血浆和尿液中发现了一种伞菌氨酸代谢物。接下来使用LC/MS研究了γ-谷氨酰转移酶（gamma-GT）作用下伞菌氨酸代谢物的结构。结果证明，对羟基苯甲基肼（HMPH）是由伞菌氨酸生成的。在给予伞菌氨酸的小鼠尿液中检测到氧化应激标志物8-羟基脱氧鸟苷（8-OHdG）。给药后，8-OHdG水平立即增至三倍，然后在48小时内降至对照水平。随后其水平再次升高，并在11天内保持高位。这些结果表明，伞菌氨酸在血浆中迅速代谢并消失，而单次给小鼠施用伞菌氨酸后，DNA损伤会持续很长时间。
