Enzymatic and non-enzymatic link components of antioxidant defence in subcellular fractions of rat liver under the influence of diethyl phthalate

Abstract

Background. The antioxidant system is one of the protective cell systems. Changes in its functioning, after the introduction of xenobiotics into the body, will determine the further course of the intensity of free radical processes. Among xenobiotics, a prominent place belongs to phthalates, in particular diethyl phthalate (DEP) – the most common group of synthetic substances that are widely used as plasticizers in various industries. Materials and Methods. For a series of experiments, white outbred rats were used, and cytosolic and microsomal fractions were isolated from the liver cells. The activity of such antioxidant enzymes as superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), glutathione peroxidase (GSH-Px, EC 1.11.1.9), glutathione S-transferase (GST, EC 2.5.1.18), and the concentration of reduced glutathione (GSH) were determined in the cytosolic fraction. GST activity was also studied in the microsomal fraction. Results and Discussion. The administration of different doses of DEP for 14 days promoted the activation of antioxidant enzymes, regardless of the dose of xenobiotic administration. The use of DEP for 21 days led to a multidirectional effect of the xenobiotic on the enzymes of the antioxidant system in liver cells. The inactivation of the studied enzymes and depletion of the GSH pool were observed when DEP was administered at a dose of 5.4 mg/kg of body weight. The activity of antioxidant enzymes in liver subcellular fractions remained at a high level compared to the control when DEP was administered at a dose of 2.5 mg/kg of body weight. It was established that the same trend of changes in GST enzyme activity was found in both the microsomal and cytosolic fractions of rat liver. The activity of the enzyme increased under the influence of both studied doses under the administration of DEP for 14 days. Administration of the xenobiotic for 21 days led to a decrease in GST activity when a high dose of DEP was administered. Conclusion. The activation of antioxidant system enzymes occurs in response to a short-term intake of DEP. With an increase in the dose and duration of administration of the studied xenobiotic, inactivation of antioxidant enzymes was detected.