TABLE 1

Metabolism dependency of the cytotoxicity, tGSH depletion, and irreversible binding of [3H]MP in rat hepatocytes demonstrated with nonspecific P450 inhibitors (ABT and SKF-525A)a

Incubation
Trypan Blue Exclusion
MTS Reduction
tGSH Content
Irreversible Binding [3H]MP
% control nmol / mg protein nmol equiv bound / mg protein
MP 29.3 (21.2) 35.0 (11.9) 16.0 (1.4) 4.56 (1.78)
MP + ABT 88.0 (12.0)** 101.2 (34.7)** 60.0 (12.9)* 0.25 (0.06)**
MP + SKF-525A
55.0 (1.4)
82.1 (23.9)*
14.0 (6.0)
0.85 (0.77)*

  • ↵ a Primary hepatocytes from male rats were preincubated for 30 min with either ABT (1 mM) or SKF-525A (50 μM) before the addition of MP (200 μM) or [3H]MP (200 μM, 1 μCi) and incubated for an additional 6 h. Cytotoxicity was assessed through diminution of trypan blue exclusion and MTS reduction. Irreversible binding of radiolabeled material to the cells was estimated by exhaustive solvent extraction. Values are expressed as mean (±S.E.M.) of three independent hepatocyte isolations.

  • ↵* p < 0.05 and

  • ↵** p < 0.01 compared to MP alone.