Gender Differences in the Effect of Antiulcer Drugs and Placenta Cryoextract on the Intensity of Lipid Peroxidation and the Activity of the Antioxidant System in Experimental Hepatitis With Ethanol-Induced Cirrhosis

Abstract

Introduction. It is well recognized that drug metabolism products in the liver can induce oxidative stress and mitochondrial dysfunction, leading to the development of hepatocellular injury. As a potential agent capable of counteracting the hepatotoxic effects of drugs, we focused our attention on a domestic biotechnological preparation – cryopreserved placental extract (CPE).
 The aim. To characterize gender differences in the effect of esomeprazole, clarithromycin, metronidazole (E/C/M), and CPE on the intensity of lipid peroxidation and the activity of the antioxidant system in tetrachloromethane (CCl4) hepatitis with a background of ethanol-induced cirrhosis (ETCM).
 Materials and methods. The study was conducted with varying levels of sex hormones on 112 male and female rats. Chronic ETCM was induced by administering a 50.0% oil solution of CCl4 at a dose of 8 ml/kg body weight of the animals twice a week, in combination with a 5.0% ethanol solution for drinking over a period of 45 days. The content of TBA-RP in liver homogenates was determined spectrophotometrically by the method described by Asakawa T. et al. Catalase activity in liver homogenates was determined spectrophotometrically according to the method of Korolyuk M.A. and co-authors.
 Results. The most pronounced increase in lipid peroxidation processes was observed in females with chronic ETCM-induced liver damage and administration of antiulcer drugs following ovariectomy, resulting in a TBA-RS content of 36.1±2.79 μmol/kg of tissue. Administration of E/C/M in animals with chronic liver damage led to a suppression of the antioxidant system, as evidenced by a decrease in catalase activity in liver tissues.
 Conclusion. The combined use of anti-ulcer drugs and CPE on the background of chronic ETCM mitigated the activation of lipid peroxidation processes, which was indicated by a statistically significant (p < 0.001) 2.7-fold lower content of TBA-RP in liver homogenates. Additionally, it was established that the administration of CPE was accompanied by a statistically significant increase in catalase activity in females, more prominently than in males. In females without changes in hormonal status, the introduction of CPE resulted in a growth (p < 0.001) of catalase activity by 75.0%, with the most significant increase observed in females after ovariectomy – catalase activity statistically significantly (p < 0.001) increased by 2.6 times compared to the indicators of females not administered with CPE. The administration of CPE in female rats without altering hormonal status was accompanied by a twofold (p < 0.01) increase in the antioxidant-prooxidant index compared to male rats, indicating more pronounced antioxidant properties of CPE in female rats.