The influence of sodium nitroprusside (SNP) on mitochondrial respiration was examined in rat liver mitochondria. The addition of SNP 1 mmol litre-1 during state 3 respiration inhibited the oxygen uptake by 63.4%. A mixture of SNP 1 mmol litre-1 and glutathione (GSH) 1 mmol litre-1 inhibited the oxygen uptake more markedly (by 75.9%). The cyanide concentrations were 0.01 mmol litre-1 with SNP alone and 0.15 mmol litre-1 with the mixture of SNP and GSH. Cyanide production from SNP in the presence of various reducing agents was studied in potassium phosphate 0.1 mol litre-1 buffer solution (pH 7.4) incubated at 37 degrees C. Cyanide was liberated markedly from SNP in the presence of GSH or ascorbate. Less cyanide was produced in the presence of NADH or NADPH. The rate of production of cyanide was dependent entirely upon the concentration of each reducing agent added. No cyanide was liberated when sodium dithionite or the oxidized forms of GSH, NAD or NADP were used. It was concluded that SNP is degradated to cyanide by a hydrogen donor and that the cyanide liberated in this manner inhibits the cytochrome oxidase activity of mitochondria in vivo.

Animals↗

PubMed1977

Macroautoradiographic study of the distribution and excretion of 14C-pentobarbitone in rats pretreated with phenobarbitone.

The distribution and excretion of pentobarbitone were studied, using macroautoradiography, in two groups of rats at times ranging from 1 min to 70 min after the i.v. injection of 100 muCi given as 30 mg/kg of 14C-pentobarbitone. In a control group, the carbon-14 concentration (concentration of pentobarbitone) in the brain remained always greater than that in heart blood (unchanged pentobarbitone and metabolites). In a group subjected to enzyme induction (pretreated with phenobarbitone), however, the carbon-14 concentration in the brain exceeded that in the heart blood initially and then decreased rapidly. In the induced group, the carbon-14 concentration in the urine and small intestine (almost all of which was metabolites) increased with time. In particular, 70 min after the injection, the carbon-14 concentration in the small intestine of the induction group was twice that of the control group. It was concluded that in the induction group the rapid decrease in carbon-14 concentration in the brain was mainly a result of an increase in the metabolic breakdown of pentobarbitone in the liver.

Animals↗

PubMed1976