THE ACTIVITY OF HEME OXYGENASE AND δ-AMINOLEVULINATE SYNTHASE IN THE RAT KIDNEY UNDER CONDITIONS OF TOXIC INJURY WITH ACETAMINOPHEN

Abstract

The aim of this work was to study the activity of δ-aminolevulinate synthase, heme oxygenase and the content of mitochondrial cytochromes in the rat kidney conditions of toxic damage with acetaminophen against the background of protein deficiency. δ-Aminolevulinate synthase activity was determined spectrophotometrically taking into account the molar extinction coefficient of 0.023·103 mol-1·cm-1, heme oxygenase activity – by the amount of bilirubin formed and expressed in nanomoles per 1 mg of protein per 1 minute. The determination of the contents of cytochromes a+a3, b, c and c1 in the suspension of isolated mitochondria was carried out by the difference spectra between the reduced and oxidized states in the region of their spectral maxima. The study was conducted on 4 groups of animals: Group I - control animals (K); II – rats kept on a low-protein diet (LPD); ІІІ – animals with acetaminophen-induced liver injury receiving complete ration (AII); IV – animals with acetaminophen-induced liver injury that were previously maintained on semi-synthetic low-protein ration (LPD/AII). It was established that under the conditions of consumption of a low-protein diet, there are no significant changes in the activities of heme oxygenase and δ-aminolevulinate synthase, but a decrease in the content of mitochondrial cytochromes a+a3, b, c, c1 is observed, which probably indicates the critical role of providing protein in the diet for the synthesis of cytochromes. At the same time, under the conditions of toxic damage by acetaminophen, regardless of whether the ration is provided with protein, there is a decrease in the activity of δ-aminolevulinate synthase by an average of 1.6 times with a simultaneous increase in the activity of heme oxygenase by approximately 1.5 times compared to the control values, which indicates an increase in the processes of heme catabolism on against the background of slowing down of its synthesis under the studied conditions. The increase in the activity of heme oxygenase against the background of the decrease in the activity of δ-aminolevulinate synthase can be considered as one of the possible mechanisms of the established decrease in the content of mitochondrial cytochromes under the conditions of acetaminophen intoxication, which in turn may further lead to a violation of the activity of the enzymes of the cytochrome part of the respiratory chain. The obtained results regarding the content of cytochromes, the activities of key enzymes of heme metabolism in the kidneys can be considered as prerequisites for deepening the energy imbalance under the conditions of toxic damage to the kidneys by acetaminophen.