Detection of malotilate toxicity in vitro with peripheral blood mononuclear cells as targets. A preliminary report.
An in vitro assessment of susceptibility to malotilate was made with peripheral blood mononuclear cells (PBMCs) as targets. PBMCs were incubated with malotilate in the presence or absence of the NADPH generating system and hepatic microsomes. Malotilate cytotoxicity to PBMCs, assessed by trypan blue dye exclusion and lactate dehydrogenase (LDH) release into the culture media, was found to be markedly increased by the addition of the NADPH generating system, indicating that metabolites play a significant role in toxicity. Once the significant role of malotilate metabolites in cytotoxicity was established, we applied this system to patients with suspected malotilate-induced liver injury. It was demonstrated that cytotoxicity was greater in PBMCs which were obtained from patients with chronic active hepatitis with a parallel malotilate-induced liver injury than in those from two different control groups; normal volunteers and patients with chronic active hepatitis who had had long-term malotilate treatment without any adverse reactions. This in vitro system seems to be of value in predicting potential malotilate toxicity in subjects who might be susceptible to this drug.
First Department of Medicine, Chiba University School of Medicine, Japan.
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F
Nomura
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Ohnishi
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Ohto
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008314:Malonates / Q000633:toxicity*; D008875:Middle Aged; D009249:NADP / Q000378:metabolism
D008314:Malonates; D009249:NADP; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate