1989 Fiscal Year Final Research Report Summary
In vitro assessment of susceptibility to toxic drug metabolites
| Project/Area Number |
62570309
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Chiba University |
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Principal Investigator |
NOMURA Fumio Ist Dept. of Med, Chiba Univ. Hospital, 医学部, 助手 (80164739)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Drug-induced liver injury / peripheral blood mononuclear cells / Malotilate / hepatic microosmes |
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| Research Abstract |
We made an in vitro assessment of susceptibility to drug metabolites with malotilate as substrate. Peripheral-blood mononulcear cells(PBMCs) were incubated with malotilate(0.12mM) in the presence of the NADPH-generating system and hepatic microsomes(O.025mg protein/ml). Cytotoxicity of malotilate to PBMCs was assessed by trypan blue dye exclusion and LDH release to the culture media, being found to be enhanced by the addition of the NADPH-generating system. The result indicated a significant role of the metabolites in toxicity. More interestingly, the cytotoxicity was remarkably greater in patients with malotilate-induced liver injury than in controls. This in vitro system may be useful in predicting potential toxicity of drugs for selected patients.
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