Gazzard B G, Hughes R D, Portmann B, Dordoni B, Williams R
Br J Exp Pathol. 1974 Dec;55(6):601-5.
In view of increasing knowledge of the mechanism of production of hepatic damage by paracetamol, and the results of recent studies suggesting a beneficial effect from cysteamine administered soon after an overdose, studies were carried out in the rat on a number of possibly protective agents, using oral paracetamol in a dose of 2·5 g/kg body weight. Histological evidence of liver damage was reproducibly obtained with corresponding reductions in the levels of cytochrome P450. This was completely prevented by prior oral administration of cysteamine in a dose of 300 mg/kg body weight. The levels of cytochrome P450 were also maintained following an intraperitoneal injection of α-tocopherol (400 mg/kg body weight) but the effect on the histological evidence of liver damage was less. The administration of glutathione, propranolol and thioctic acid did not prevent the liver damage, although with these agents—except glutathione—the number of wedge shaped areas of necrosis (infarcts) in the liver was reduced.
鉴于对扑热息痛导致肝损伤机制的认识不断增加，以及近期研究结果表明过量服用后不久给予半胱胺有有益效果，于是以2.5 g/kg体重的口服扑热息痛对大鼠进行了多项可能具有保护作用药物的研究。可重复性地获得了肝损伤的组织学证据，同时细胞色素P450水平相应降低。预先口服300 mg/kg体重的半胱胺可完全预防这种情况。腹腔注射α-生育酚（400 mg/kg体重）后细胞色素P450水平也得以维持，但对肝损伤组织学证据的影响较小。给予谷胱甘肽、普萘洛尔和硫辛酸并不能预防肝损伤，不过使用这些药物（除谷胱甘肽外）时，肝脏中楔形坏死区域（梗死灶）的数量有所减少。
