The detoxication of aflatoxin B1 with glutathione in the rat.

1. The deactivation of aflatoxin B1 by glutathione (GSH) has been investigated in rat. Binding of metabolites of aflatoxin B1 to [3H]glutathione in vitro with rat liver microsomes is insignificant. Incubation with rat liver 10 000 g supernatant results in increased binding. Under identical conditions, benzo(a)pyrene metabolites are bound to [3H]glutathione much more than is aflatoxin B1. 2. Pre-treatment of rats with aflatoxin 1 (2 mg/kg) caused depletion in GSH of rat liver with a minimum at 6 h but returning to above normal at 24 h. GSH S-transferase activity was marginally increased at 6 h also and returned to normal at 24 h. 3. Kidney GSH was not significantly decreased, but kidney GSH S-transferase activity showed a sudden increase in 6 h, returning to almost normal at 24 h. 4. Pre-treatment with benzo(a)pyrene (2 mg/kg) caused greater depletion of hepatic GSH than occurred with aflatoxin B1 but did not show any effect on kidney GSH. 5. Hepatic and kidney GSH S-transferase in benzo(a)pyrene-treated rats showed greatest activity at 2 h followed by a gradual fall through 24 h. 6. GSH was therefore a less efficient nucleophile for aflatoxin B1 metabolites than for benzo(a)pyrene metabolites.