Tag Archives: diethyl phthalate
Cytochrome P450 dependent free radical processes in the liver microsomes of rats administered diethyl phthalate
О. V. Kеtsa*, М. М. Маrchenko
Educational and Scientific Institute of Biology, Chemistry and Natural Resources,
Yuriy Fedkovych Chernivtsi National University, Chernivtsi, Ukraine;
*e-mail: o.ketsa@chnu.edu.ua
Received: 28 May 2025; Revised: 03 July 2025;
Accepted: 12 September 2025; Available on-line: 17 September2025
Diethyl phthalate (DEP) is widely used as a plasticizer and aromatic additive in various consumer products. Biotransformation of this xenobiotic occurs through the cytochrome P450 (CYP) -hydroxylating system, the catalytic cycle of which is accompanied by ROS generation in uncoupling reactions. The present study investigated the effects of DEP administration on the CYP-dependent ROS generation and lipid peroxidation in the rat liver microsomes. The experiment was conducted on three groups of purebred white rats: control (intact animals); rats orally administered with DEP at a dose of 2.5 or 5.4 mg/kg b.w per day for 21 days. CYP-mediated ROS generation was initiated by adding 0.24 μmol/l NADPH to the incubation mixture. It was found that daily administration of DEP at a dose of 2.5 mg/kg led to an increase in the rate of O2•– formation, H2O2 content, and intensification of lipid peroxidation in the liver microsomes only on the 21st day of the experiment. In contrast, administration of DEP at a dose of 5.4 mg/kg resulted in increased content of primary, secondary and final lipid peroxidation products as early as on the 14th day of xenobiotic exposure, indicating a dose- and time-dependent effect of DEP on the oxidative stress intensity in liver microsomes.
Free radical processes in the liver mitochondria of rats exposed to diethyl phthalate
O. V. Ketsa*, A. P. Husliakova, M. M. Marchenko
Yuriy Fedkovych Chernivtsi National University, Chernivtsi, Ukraine;
*e-mail: o.ketsa@chnu.edu.ua
Received: 11 October 2023; Revised: 28 November 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024
Diethyl phthalate (DEF) is a synthetic chemical widely used as plasticizer and additive in personal care and pharmaceutical products. Low-dose exposure to this xenobiotic over a long period contributes to its intake into the human body in a high doses. To date, studies of DEF influence on free radical processes in liver cells, in which it is not only metabolized but can also have a prooxidant effect, remain limited. The aim of our research was to determine ROS formation, the intensity of oxidative modification of proteins (OMP) and proteolytic activity in the mitochondrial fraction of liver tissue of rats exposed to diethyl phtalate. The experimental white outbred rats were divided into three groups: I – intact animals (control), II and III – rats administered DEF orally for three weeks at a doses that reflect the dose levels received by humans, namely 2.5 and 5.4 mg/kg b.w. respectively. The animals were euthanized on the 14th and 21st day after xenobiotic administration. The mitochondrial fraction from the rat liver was isolated and the level of superoxide and hydroxyl radicals, protein carbonyl derivatives, SH-groups and Schiff bases was determined. Proteolytic activity was assessed in the test of hemoglobin cleavage. It was shown that administration of DEF in a dose of 2.5 mg/kg initiated ROS generation and OMP intensification in the rat liver mitochondria only with prolonged administration for 21 days, whereas its administration in a dose of 5.4 mg/kg led to intensification of these processes already on day 14th followed by further amplification on day 21st. The activity of proteolytic enzymes in the mitochondrial fraction was found to be depended on the degree of DEF–induced OMP and was increased with minor OMP intensification but decreased with significant intensification of proteins free radical oxidation.