Acute effects of carbon monoxide and cyanide on hepatic mitochondrial function

The effects of carbon monoxide and cyanide on the hepatic redox state and energy charge were investigated. Rats were used for the experiment under pentobarbital anesthesia. Immediately after laparotomy, a rat was placed in an animal chamber made of a transparent plastic box and exposed to a test gas for 3 min. Every test gas was produced in a gas chamber connected to the animal chamber with a flexible tube. HCN was produced from NaCN and H2SO4. In the CO inhalation experiment, various amounts of CO were introduced into the gas chamber. Immediately after an exposure, about 2 g liver was frozen in situ with a precooled clamp. Oozed blood from the wound surface was sampled. Concentrations of ATP, ADP, AMP, acetoacetate, and beta-hydroxybutyrate in hepatic mitochondria were determined, and the redox state and the energy charge were calculated. For cyanide as well as CO, significant negative correlations were found between the concentration in the blood and the redox state. The same held true for the energy charge. The redox state showed a slight increase at low concentrations of both gases; however, thereafter it began to decrease sharply with increases in concentrations. When concentrations of the toxicant in the blood reached certain levels, a kind of turning point, beyond which the redox state does not decrease any more, was observed. It was about 40% for HbCO and about 2.0 micrograms/ml for cyanide, and the points seemed to be related to the concentrations, beyond which cells are irreversibly damaged. On the other hand, the energy charge did not change at low concentrations. With an increase in toxicant concentrations, the energy charge decreased drastically. The rate of decrease in the energy charge became higher when blood concentrations exceeded certain levels. It was about 40% for HbCO and 2.0 micrograms/ml for cyanide. The presence of low levels of blood cyanide did not affect the relationship between the energy charge and the HbCO concentration.