El-Hage A N, Herman E H, Ferrans V J
Toxicology. 1983 Nov;28(4):295-303. doi: 10.1016/0300-483x(83)90003-3.
The protective activity of 1,2-bis(3,5-dioxopiperazin-l-yl)propane (ICRF-187) and dimethyl sulfoxide (DMSO) was tested against acetaminophen-induced hepatotoxicity. Male Syrian golden hamsters injected intraperitoneally between 18:00 h and 20:00 h for 2 consecutive days with acetaminophen (N-acetyl-p-aminophenol) (300 mg/kg) displayed signs of hepatotoxicity as evidenced by increases in enzyme activity and cellular damage. Forty-eight hours after the second acetaminophen dose, the activities of serum glutamic-pyruvic transaminase and alkaline phosphatase were increased compared with levels found in hamsters given only saline. In addition, hepatocellular necrosis was evident in acetaminophen-treated animals. ICRF-187 (300 mg/kg) given 1 h before acetaminophen attenuated the increases in enzyme activities, and both DMSO (7.3 g/kg) and ICRF-187 reduced the incidence and severity of acetaminophen-induced hepatocellular injury. Both ICRF-187 and DMSO are capable of altering free radical-mediated toxicity in other experimental systems. Whether these compounds reduce acetaminophen-induced liver toxicity by a similar mechanism remains to be determined.
测试了1,2-双(3,5-二氧代哌嗪-1-基)丙烷(ICRF-187)和二甲基亚砜(DMSO)对乙酰氨基酚诱导的肝毒性的保护活性。雄性叙利亚金黄地鼠在18:00至20:00之间连续2天腹腔注射乙酰氨基酚(N-乙酰对氨基酚)(300mg/kg)，表现出肝毒性迹象，酶活性增加和细胞损伤证明了这一点。第二次给予乙酰氨基酚48小时后，与仅给予生理盐水的仓鼠相比，血清谷丙转氨酶和碱性磷酸酶的活性增加。此外，在乙酰氨基酚处理的动物中肝细胞坏死明显。在给予乙酰氨基酚前1小时给予ICRF-187(300mg/kg)可减轻酶活性的增加，并且DMSO(7.3g/kg)和ICRF-187均降低了乙酰氨基酚诱导的肝细胞损伤的发生率和严重程度。ICRF-187和DMSO在其他实验系统中均能够改变自由基介导的毒性。这些化合物是否通过类似机制降低乙酰氨基酚诱导的肝毒性仍有待确定。
