Effect of Aspergillus fumigatus endotoxin on the respiration and phosphorylation of kidney tissue

The nephrotoxin in mycelial extracts of Aspergillus fumigatus produces morphological changes resembling those observed in mercuric chloride poisoning in vivo. The toxic factor has been purified by ammonium sulfate precipitation and chromatographic fractionation. This paper presents the effects of purified toxic extracts on mouse kidney homogenate and mitochondria in vitro.Homogenate respiration rate was a function of substrate concentration. In the presence of succinate or ascorbate, respiration increased to a high plateau with increasing substrate concentration, whereas with citrate, malate, or other pyridine nucleotide-linked substrates, the rate increased to a low maximum and then decreased.At optimal concentration of substrates, respiration was stimulated by low concentrations of toxin but depressed by high concentrations. A much lower concentrations of toxin produced these effects with citrate than with ascorbate or succinate. Similar patterns of stimulation and depression were obtained with 2,4-dinitrophenol.Complete uncoupling of oxidative phosphorylation, as judged from the P:O ratio, was evident with both succinate and citrate at higher toxin concentrations. This uncoupling effect disappeared when nephrotoxicity was inactivated by heat, although some respiratory inhibition effect persisted. The previously reported hypercitricemia after intravenous administration of a lethal dose of toxin to mammals is probably due to suppression of citrate oxidation.