Kitamura Y, Kamisaki Y, Itoh T
Department of Clinical Pharmacology, Tottori University School of Medicine, Yonago, Japan.
J Pharmacol Exp Ther. 1989 Aug;250(2):667-71.
The hepatoprotective effects of cystathionine, as a prodrug of cysteine release, were examined in rodents. When cystathionine (100 mg/kg) was administered i.p. in rats, it was eliminated from rat serum with a biological half-life of 1.19 +/- 0.23 hr. Subsequent to the decrease of serum cystathionine, the concentration of cyst(e)ine increased up to 14.5 +/- 1.2 mg/l, and then decreased with a half-life of 4.12 +/- 0.82 hr. The concomitant administration of taurine (100 mg/kg) did not change the half-life of cystathionine (1.42 +/- 0.33 hr), but significantly increased the half-life of cyst(e)ine (19.1 +/- 0.56 hr). This effect of taurine was also observed when cysteine (100 mg/kg) was administered to rats. The liver injury was induced by the i.p. injection of acetaminophen (5.0 mmol/kg). The mortality rates, serum alanine and aspartate aminotransferase activities and the histological analysis of the livers, which were obtained from living mice, were examined 22 hr after the injections. Two administrations of cystathionine (5.0 mmol/kg x 2), one at 20 min before and one 20 min after the acetaminophen injection, prevented the acetaminophen-induced hepatic necrosis, completely. The coadministration of taurine increased the hepatoprotective activity of cystathionine, even at the low dosages (0.18 and 0.55 mmol/kg x 2). Moreover, the treatments using cystathionine, with and without taurine, restored the hepatic glutathione levels to 2.27 +/- 0.23 and 1.80 +/- 0.27 mumol/g, respectively. These levels had been depleted by acetaminophen injection to 0.96 +/- 0.18 mumol/g, 2 hr after the injection. Propargylglycine, an inhibitor of cystathionase, abolished the hepatoprotective effects of cystathionine, although it could not affect the action of cysteine.(ABSTRACT TRUNCATED AT 250 WORDS)
作为半胱氨酸释放前体药物的胱硫醚对啮齿动物的肝脏保护作用进行了研究。当向大鼠腹腔注射胱硫醚（100mg/kg）时，其从大鼠血清中消除，生物半衰期为1.19±0.23小时。血清胱硫醚浓度下降后，胱氨酸浓度升高至14.5±1.2mg/L，然后以4.12±0.82小时的半衰期下降。同时给予牛磺酸（100mg/kg）并未改变胱硫醚的半衰期（1.42±0.33小时），但显著延长了胱氨酸的半衰期（19.1±0.56小时）。当向大鼠注射半胱氨酸（100mg/kg）时也观察到了牛磺酸的这种作用。通过腹腔注射对乙酰氨基酚（5.0mmol/kg）诱导肝损伤。注射后22小时检查从存活小鼠获得的死亡率、血清丙氨酸和天冬氨酸转氨酶活性以及肝脏的组织学分析。在对乙酰氨基酚注射前20分钟和注射后20分钟各给予一次胱硫醚（5.0mmol/kg×2），可完全预防对乙酰氨基酚诱导的肝坏死。即使在低剂量（0.18和0.55mmol/kg×2）下，同时给予牛磺酸也可增强胱硫醚的肝脏保护活性。此外，使用胱硫醚（加或不加牛磺酸）治疗分别将肝脏谷胱甘肽水平恢复至2.27±0.23和1.80±0.27μmol/g。注射对乙酰氨基酚2小时后，这些水平已降至0.96±0.18μmol/g。胱硫醚酶抑制剂炔丙基甘氨酸消除了胱硫醚的肝脏保护作用，尽管它不影响半胱氨酸的作用。（摘要截断于250字）
