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 21^st 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 14^th day of xenobiotic exposure, indicating a dose- and time-dependent effect of DEP on the oxidative stress intensity in liver microsomes.