Hu J J, Yoo J S, Lin M, Wang E J, Yang C S
Department of Chemical Biology and Pharmacognosy, Rutgers University, Piscataway, NJ 08855-0789, USA.
Food Chem Toxicol. 1996 Oct;34(10):963-9. doi: 10.1016/s0278-6915(96)00057-9.
Diallyl sulfide (DAS), a major flavour component of garlic, is known to modulate drug metabolism and may protect animals from chemically induced toxicity and carcinogenesis. In this study the effects of DAS on the oxidative metabolism and hepatotoxicity induced by acetaminophen (APAP) in rats were investigated. In the hepatotoxicity evaluation of Fischer 344 rats there was a dose-dependent increase in the odds of mortality rate by APAP (P = 0.009); DAS treatment significantly protected rats from APAP-related mortality (P = 0.026). Liver toxicity determined by lactate dehydrogenase activity was significantly increased by APAP treatment (0.75 g/kg). Pretreatment with DAS protected animals from APAP-induced liver toxicity in a time- and dose-dependent fashion. Treatment of DAS (50 mg/kg) 3 hr after APAP dosing significantly (P < 0.05) protected rats from APAP-induced liver toxicity. The metabolism of APAP (50 microM) in vitro was significantly inhibited by DAS (0.3-1 mM) in liver microsomes isolated from F344 rats. As the effect of DAS on APAP-induced hepatotoxicity in vivo was observed only when DAS was administered before or shortly after (< 3 hr) APAP dosing, data suggested that the protective effect of DAS is mainly at the metabolic activation step of APAP. However, the possibility that DAS may also have effects on other drug metabolism systems, such as glutathione (GSH) and glutathione S-transferases, cannot be ruled out.
二烯丙基硫醚（DAS）是大蒜的一种主要风味成分，已知其可调节药物代谢，并可能保护动物免受化学诱导的毒性和致癌作用。在本研究中，研究了DAS对大鼠对乙酰氨基酚（APAP）诱导的氧化代谢和肝毒性的影响。在对Fischer 344大鼠的肝毒性评估中，APAP导致的死亡率几率呈剂量依赖性增加（P = 0.009）；DAS治疗显著保护大鼠免受与APAP相关的死亡（P = 0.026）。通过乳酸脱氢酶活性测定的肝毒性在APAP治疗（0.75 g/kg）后显著增加。DAS预处理以时间和剂量依赖性方式保护动物免受APAP诱导的肝毒性。在APAP给药后3小时给予DAS（50 mg/kg）显著（P < 0.05）保护大鼠免受APAP诱导的肝毒性。在从F344大鼠分离的肝微粒体中，DAS（0.3 - 1 mM）显著抑制APAP（50 microM）的体外代谢。由于仅在APAP给药前或给药后不久（< 3小时）给予DAS时才观察到DAS对体内APAP诱导的肝毒性的影响，数据表明DAS的保护作用主要在APAP的代谢活化步骤。然而，不能排除DAS也可能对其他药物代谢系统产生影响的可能性，例如谷胱甘肽（GSH）和谷胱甘肽S-转移酶。
