Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity

被引：235

作者：

Ghanem, Carolina I. ^{[1
,2
]}

Perez, Maria J. ^{[3
]}

Manautou, Jose E. ^{[4
]}

Mottino, Aldo D. ^{[5
]}

机构：

[1] Univ Buenos Aires, CONICET, Fac Farm & Bioquim, Inst Invest Farmacol ININFA, Buenos Aires, DF, Argentina

[2] Univ Buenos Aires, Catedra Fisiopatol, Fac Farm & Bioquim, Buenos Aires, DF, Argentina

[3] Univ Buenos Aires, CONICET, Inst Quim & Fis Quim Biol IQUIFIB, Catedra Quim Biol Patol,Fac Farm & Bioquim, Buenos Aires, DF, Argentina

[4] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT USA

[5] Univ Nacl Rosario, CONICET, Inst Fisiol Expt IFISE, Fac Ciencias Bioquim & Farmaceut, Rosario, Santa Fe, Argentina

来源：

PHARMACOLOGICAL RESEARCH | 2016年 / 109卷

基金：

美国国家卫生研究院;

关键词：

Acetaminophen; Hepatic toxicity; trpv1; Necroptosis; Caspase; DAMPs; MITOCHONDRIAL PERMEABILITY TRANSITION; INDUCED HEPATIC-NECROSIS; N-TERMINAL KINASE; CULTURED MOUSE HEPATOCYTES; CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; INDUCED HEPATOTOXICITY; OXIDANT STRESS; CELL-DEATH; CEREBROSPINAL-FLUID;

D O I：

10.1016/j.phrs.2016.02.020

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Acetaminophen (APAP) is a well-known analgesic and antipyretic drug. It is considered to be safe when administered within its therapeutic range, but in cases of acute intoxication, hepatotoxicity can occur. APAP overdose is the leading cause of acute liver failure in the northern hemisphere. Historically, studies on APAP toxicity have been focused on liver, with alterations in brain function attributed to secondary effects of acute liver failure. However, in the last decade the pharmacological mechanism of APAP as a cannabinoid system modulator has been documented and some articles have reported "in situ" toxicity by APAP in brain tissue at high doses. Paradoxically, low doses of APAP have been reported to produce the opposite, neuroprotective effects. In this paper we present a comprehensive, up-to-date overview of hepatic toxicity as well as a thorough review of both toxic and beneficial effects of APAP in brain. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：119 / 131

页数：13

共 139 条

[1]

AGGARWAL S, 1994, HEPATOLOGY, V19, P80, DOI 10.1002/hep.1840190114

[2] Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation [J].