Hepatotoxicity of Flunitrazepam and Alcohol In Vitro

Flunitrazepam (FNZ) is a benzodiazepine derivative more potent than diazepam. FNZ abuse in the US has emerged in the last few years and has a growing popularity among young people and drug abusing populations. Ethanol (EtOH) consumption with FNZ enhances euphoria and onset of action. It is postulate...

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Bibliographic Details
Published in:Toxicology in vitro 1999-06, Vol.13 (3), p.393-401
Main Authors: Assaf, M.S, Abdel-Rahman, M.S
Format: Article
Language:English
Subjects:
Biological and medical sciences
Drug addictions
Medical sciences
Toxicology
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Summary:Flunitrazepam (FNZ) is a benzodiazepine derivative more potent than diazepam. FNZ abuse in the US has emerged in the last few years and has a growing popularity among young people and drug abusing populations. Ethanol (EtOH) consumption with FNZ enhances euphoria and onset of action. It is postulated that FNZ and EtOH cause liver cell injury. In this study, hepatocytes are employed to study the hepatotoxicity of FNZ, EtOH and their combination (FNZ-EtOH). Hepatocytes (2×10 6 cells/ml) isolated from male Sprague–Dawley rats were exposed to saline, FNZ, EtOH or FNZ-EtOH in combination. The uptake of 0.4% trypan blue and the leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes into the incubation media were used to assess cell membrane damage of hepatocytes. Where metabolism of FNZ is nearly complete through several hepatic pathways, animal pretreatment with Phenobarbital was used to study the effect of microsomal enzyme induction on cellular injury. FNZ (0.16 m m), EtOH (32.56 m m) or their combination caused a significant ( P
ISSN:0887-2333
1879-3177
DOI:10.1016/S0887-2333(99)00004-1