The Detoxication of Aflatoxin B₁ with Glutathione in the Rat

Abstract

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 10000g 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 B₁ (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 2h 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.