Activity of enzymes of tyrosine metabolism in the rat liver under the conditions of acetaminophen-induced hepatitis on the background of protein deficiency

The contribution of the mis-metabolism of individual amino acids to the development of drug-induced damage to liver cells remains unexplored. The aim of the present study was to investigate the changes in liver tyrosine level and activity of the enzymes of its metabolism: tyrosine aminotransferase, 4-hydroxyphenylpyruvate dioxygenase, aldehyde dehydrogenase ALDH3A1 under the conditions of acetaminophen-induced hepatitis on the background of protein deficiency. Determination of tyrosine in deproteinized with 6% sulfosalicylic acid extracts of the liver tissue was performed using the automatic analyzer of amino acids T-339 (“Microtechnology”, Czech Republic). The enzyme activity was determined by spectrophotometric method – tyrosine aminotransferase by the amount of 4-hydroxybenzaldehyde, which has a maximum absorption at 330 nm, 4-hydroxyphenylpyruvate dioxygenase – by the colored product intensity at λ 336 nm, aldehyde dehydrogenase ALDH3A1 activity was measured at 340 nm wavelength. Results have shown that in animals with toxic liver injury which were maintained in conditions of alimentary protein deficiency, a 5-fold decrease in tyrosine level in the liver was observed. At the same time in animals of this group there was a decrease in TAT activity by 1.6 times, a 4-fold decrease in activity of aldehyde dehydrogenase ALDH3A1 and increase in the activity of 4-hydroxyphenylpyruvate dioxygenase by 2.5 time comparing to control parameters. Conclusion was made, that alimentary protein deficiency is a factor leading to an intensification of tyrosine metabolism disturbances in animals with toxic liver injury. The pronounced exhaustion of the tyrosine pool is accompanied by the activation of the homogentisate pathway of its metabolism, as evidenced by the increase in the activity of 4-hydroxyphenylpyruvate dioxygenase and simultaneous reduction in the aldehyde dehydrogenase ALDH3A1activity. The established changes open prospects to study the possible targets for the exogenous correction of metabolic disorders under the conditions of intoxication with acetaminophen, especially in people with protein deficiency.

Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency

Activity of isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, malate dehydrogenase, and the NAD+/NADН ratio were studied in the liver mitochondrial fraction of rats with toxic hepatitis induced by acetaminophen under conditions of alimentary protein deprivation. Acetaminophen-induced hepatitis was characterized by a decrease of isocitrate dehydrogenase, a-ketoglutarate dehydrogenase and malate dehydrogenase activities, while the mitochondrial NAD+/NADН ratio remained at the control level. Modeling of acetaminophen-induced hepatitis in rats with alimentary protein caused a more pronounced decrease in the activity of NAD+-dependent dehydrogenases studied and a 2.2-fold increase of the mitochondrial NAD+/NADН ratio. This suggests that alimentary protein deprivation potentiated drug-induced liver damage