BIOCHEMICAL INDICATORS OF LIVER FUNCTIONAL STATE IN RATS UNDER EXPOSURE TO THE CYTOTOXIC XENOBIOTIC DIETHYL PHTHALATE

Abstract

Background. The widespread use of phthalates, including diethyl phthalate (DEP), in industrial and household products raises concerns about their potential hepatotoxic effects. The liver, as the central organ of detoxification and metabolism, is particularly vulnerable to the toxic effects of xenobiotics, especially DEP. Objective: this study aimed to assess the indicators of liver functional state in rats under exposure to the cytotoxic xenobiotic diethyl phthalate.
Materials and Methods. The experiment was conducted on adult white rats, which were divided into three groups: the control group and two experimental groups that received DEP orally at doses of 2.5 mg/kg and 5 mg/kg for 21 days. Biochemical markers of hepatocyte damage and cholestasis, including the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), the levels of total and direct bilirubin, as well as the albumin-to-globulin ratio, were analyzed in blood serum using standard spectrophotometric and automated methods.
Results and Discussion. It was found that administration of DEP led to dose- and time-dependent changes in markers of liver functional state. At a dose of 5 mg/kg, DEP caused a significant increase in ALT and AST activity as early as on day 14 of xenobiotic exposure, indicating hepatocyte damage. By day 21 of the experiment, both doses of the xenobiotic induced a marked elevation in all studied serum markers of liver function. At the same time, increased GGT and ALP activity, along with elevated levels of total and direct bilirubin, indicated the development of cholestatic dysfunction. In addition, a decrease in the albumin-to-globulin ratio in both DEP-treated groups over three weeks indicated impaired protein-synthesizing function of the liver.
Conclusion. The xenobiotic DEP induces a combined hepatocellular and cholestatic liver dysfunction in a dose- and time-dependent manner. The observed biochemical changes indicate oxidative stress and disrupted energy metabolism as key mechanisms underlying DEP-induced hepatotoxicity. The obtained results highlight the importance of further research into the molecular pathways of phthalate-induced liver injury and support the development of biocompatible materials and early diagnostic tools for hepatotoxicity.