Alteration of energy-linked functions in rat hepatic mitochondria following aflatoxin B1 administration.

Respiratory activity in hepatic mitochondria have been examined following administration of the carcinogen aflatoxin, (AFB1) to rats. Measurement in isolated mitochondria of respiration rates in presence of ADP (state 3) and after its depletion (state 4) revealed that these rates were not significantly altered in livers of rats obtained 4-8 hours after single injection of AFB1 (7 mg/kg of body weight). After 12-24 hours, however, a generalized inhibition in state 3 respiration rate and ADP phosphorylation rate had been evident with several FAD- and NAD-linked oxidizing substrates. But the ADP:0 ratio did not show any alteration. State 4 respiration rates, on the other hand, were increased remarkably (38-94% depending on substrate used), thereby recording in each case a decrease in respiratory control ratio (state 3:state 4 ratio), indicating probable damage to mitochondrial membrane as a result of AFB1 ingestion. This was also evident from greater basal ATPase and Mg(2+)-ATPase activities and low total ATPase activity. After 48-72 hours of AFB1 treatment, the respiratory rates as well as the ATPase activities returned to normal levels, suggesting probable recovery of mitochondrial functions from the toxic effects of AFB1.