Tag Archives: acetaminophen
Cytochrome P450 enzymes activity in rat liver under conditions of toxic injury and partial hepatectomy
Н. P. Kopylchuk, I. M. Nykolaichuk, М. S. Ursatyi*
Educational and Scientific Institute of Biology, Chemistry and Natural Resources,
Yuriy Fedkovych Chernivtsi National University, Chernivtsi, Ukraine;
*e-mail: m.ursatyi@chnu.edu.ua
Received: 26 December 2024; Revised: 23 February 2025;
Accepted: 25 April 2025; Available on-line: 12 May 2025
The unique liver ability for reparative regeneration plays a decisive role in restoring its homeostatic potential. However, in certain clinical situations, in particular, due to the damage caused by toxicants of a medicinal origin, the regenerative response may be impaired. Uncontrolled use of nonsteroidal anti-inflammatory drug paracetamol (acetaminophen, APAP) is among the leading causes of acute liver failure. The study focuses on evaluating of p-hydroxylase, N-demethylase, N-oxygenase activity of cytochrome P450 (CYP) enzymes as well as the CYP content in the microsomal fraction of the liver of rats subjected to partial hepatectomy following acute acetaminophen-induced toxic injury. White non-linear rats were divided into two groups: with partial hepatectomy (resection of 2/3 of liver tissue) and with partial hepatectomy following oral acetaminophen administration for 2 days at a dose of 1250 mg/kg b. w. Experimental data were obtained at 0 (control), 24, 48, 72 and 168 h after hepatectomy. The regeneration process at the early stages after partial hepatectomy in animals that were not exposed to APAP injury was accompanied by the suppression of aniline p-hydroxylase and dimethylaniline N-demethylase activity, along with a simultaneous decrease in cytochrome P450 content against the background of a compensatory increase of N-oxygenase activity. Liver tissue recovery after partial hepatectomy in animals with APAP injury was characterized by an increase in cytochrome P450 content along with concurrent activation of aromatic hydroxylation, N-dealkylation, and N-oxidation reactions throughout the entire regenerative period. The data obtained indicate the initiating of competing pathways of acetaminophen detoxification and/or toxification at different time intervals during the process of liver reparative regeneration.
Indexes of citrulline metabolism in rat liver under the toxic injury against the background of alimentary protein deficiency
H. P. Kopylchuk, I. M. Nykolaichuk, I. S. Lylyk
Yuriy Fedkovych Chernivtsi National University, Ukraine;
Institute of Biology, Chemistry and Bioresources, Chernivtsi, Ukraine;
e-mail: g.kopilchuk@chnu.edu.ua
Received: 29 May 2019; Accepted: 29 November 2019
It is known that citrulline is converted into arginine in the series of metabolic transformations. Results of our previous studies showed that acetaminophen-induced toxic injury on the background of the alimentary deprivation of protein is accompanied by a decrease in arginine level in rat hepatocytes, but citrulline liver metabolism at these conditions remains incompletely clear. In this work, the content of citrulline in the rat liver mitochondrial and cytosolic fractions and the activity of citrulline-degrading enzymes – argininosuccinate synthase and argininosuccinate lyase were investigated. It was found that in the mitochondrial fraction a maximal reduction of the citrulline levels occurred after administration of acetaminophen toxic doses regardless of the protein amount in the ration, while in the cytosolic fraction the alimentary protein deficiency was a key factor in decreasing the activity of argininosuccinate synthase and arginino-succinate lyase. The data obtained indicated the disturbances of the urea cycle functioning and explained the decrease of L-arginine level in hepatocytes in conditions of acetaminophen-induced toxic injury against the background alimentary protein deficiency.
Rat liver arginase system under acetaminophen-induced toxic injury and protein deprivation
H. P. Kopylchuk, I. M. Nykolaichuk, O. M. Zhuretska
Yuriy Fedkovych Chernivtsi National University, Ukraine;
Institute of Biology, Chemistry and Bioresourses, Chernivtsi, Ukraine;
e-mail: kopilchuk@gmail.com
Arginase activity and L-arginine content in both cytosolic and mitochondrial fractions of rat liver cells under the conditions of toxic injury on the background of protein deprivation was studied. The most significant reduction of arginase activity in liver cells and depletion of L-arginine pool was found in rats with toxic acetaminophen-induced liver injury maintained on the ration balanced by all nutrients as well as in protein deficiency rats. It was concluded that reduction of the arginase activity in the cytosolic fraction of rat liver cells, combined with simultaneous decrease of L-arginine content, may be considered as one of the mechanisms of ornithine cycle disturbance. The decline of activity of mitochondrial isoform of arginase II, for certain, is related with activation of NO-synthase system.
Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency
G. P. Kopylchuk, O. M. Voloshchuk
Yuriy Fedkovych Chernivtsi National University
Institute of Biology, Chemistry and Natural Resources, Ukraine;
e-mail: kopilchuk@gmail.com
The rate of superoxide anion radical, hydroxyl radical and hydrogen peroxide generation, the level of oxidative modification of mitochondrial proteins in the liver of rats with toxic hepatitis was investigated on the background of alimentary protein deficiency. We did not find significant increases of the intensity of free radical processes in liver mitochondria of rats maintained on the protein-deficient ration. The most significant intensification of free radical processes in liver mitochondria is observed under the conditions of toxic hepatitis, induced on the background of alimentary protein deprivation. Under these conditions the aggravation of all studied forms of reactive oxygen species generation was observed in liver mitochondria. The generation rates were increased as follows: O2 – by 1.7 times, Н2О2 – by 1.5 times, •ОН – practically double on the background of accumulation of oxidized mitochondria-derived proteins. The established changes in thiol groups’ redox status of respiratory chain proteins insoluble in 0.05 M sodium-phosphate buffer (pH 11.5), and changes of their carbonyl derivatives content may be considered as one of the regulatory factors of mitochondrial energy-generating function.