Cytotoxicity induced by the combination of valproic acid and tumor necrosis factor-α: Implication for valproic acid-associated hepatotoxicity syndrome
作者： Cai-ping Yao , Gary G Mather , Jeffrey R Stephens , René H Levy
DOI: 10.1016/S0006-2952(99)00108-2
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摘要: Abstract A previous study showed that valproic acid (VPA) and tumor necrosis factor-α (TNF-α) exhibit synergistic toxicity (lethality) in Sprague–Dawley Wistar rats. The present investigated a possible mechanism for this synergy using an vitro system. Incubation of human U937 cells with 1 mM VPA or 0.001 ng/mL TNF-α alone had negligible effect on cytotoxicity (less than 7%). However, the combination two drugs significantly increased up to 34%. Chronic treatment 48 hr reduced protein kinase C (PKC) activity. Further, PKC selective inhibitor Go6976 potentiated VPA-induced TNF-α-induced cytotoxicity, whereas activator phorbol-12-myristate-13-acetate provided significant protection against associated TNF-α. These results suggest synergism exhibited by may be mediated through attenuation
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