Piperno E, Mosher A H, Berssenbruegge D A, Winkler J D, Smith R B
Pediatrics. 1978 Nov;62(5 Pt 2 Suppl):880-9.
Acute acetaminophen intoxication was studied in the dog to characterize pathogenesis and in the mouse as a model for antidotal research. In the dog, overt toxicity was manifested principally by cyanosis, facial and paw edema, gastrointestinal disturbance, and coma. Typical laboratory findings were methemoglobinemia, hemoconcentration, leukocytosis, and hepatic centrolobular necrosis. In the mouse, physical signs of acetaminophen overdose appeared to be central in origin; sequelae included anemia, leukopenia, thrombocytopenia, and hepatic centrolobular necrosis. The antidotal profile of acetylcysteine in mice was characterized. When acetylcysteine therapy was instituted early (one hour after acetaminophen overdose), it conferred dose-related protection from lethality coupled with hepatoprotection, as judged from transaminase activity. When acetylcysteine therapy was instituted relatively late (4 1/2 hours after acetaminophen overdose), its beneficial effect on survival persisted but was unaccompanied by distinct hepatoprotection, indicating that SGPT activity was an unreliable prognostic indicator. Acetylcysteine was well tolerated in mice even when administered in the presence of preexisting acetaminophen-induced liver damage.
对狗进行了急性对乙酰氨基酚中毒研究以确定其发病机制，并以小鼠作为解毒研究的模型。在狗身上，明显的毒性主要表现为发绀、面部和爪子水肿、胃肠道紊乱和昏迷。典型的实验室检查结果是高铁血红蛋白血症、血液浓缩、白细胞增多和肝小叶中心坏死。在小鼠身上，对乙酰氨基酚过量的体征似乎起源于中枢；后遗症包括贫血、白细胞减少、血小板减少和肝小叶中心坏死。对小鼠中乙酰半胱氨酸的解毒情况进行了表征。当早期（对乙酰氨基酚过量后1小时）开始使用乙酰半胱氨酸治疗时，根据转氨酶活性判断，它可提供与剂量相关的对致死性的保护以及肝脏保护作用。当相对较晚（对乙酰氨基酚过量后4.5小时）开始使用乙酰半胱氨酸治疗时，其对存活的有益作用仍然存在，但没有明显的肝脏保护作用，这表明谷丙转氨酶活性是一个不可靠的预后指标。即使在存在预先存在的对乙酰氨基酚诱导的肝损伤的情况下给予乙酰半胱氨酸，小鼠对其耐受性也良好。
