Parameters of Oxidative Stress and Endogenous Intoxication in Experimental Modeling of Destructive Cholecystitis

Acute destructive cholecystitis (ADC) remains a serious problem in abdominal surgery with high rates of complications and mortality. The traditional view of its pathogenesis as a consequence of obstruction and infection is insufficient. Modern data point to the key role of systemic disorders, particularly oxidative stress and endogenous intoxication, but their temporal dynamics and interrelationship in ADC are poorly understood. A comprehensive study of the temporal dynamics of oxidative stress (OS) and endogenous intoxication (EI) parameters in an experimental model of destructive cholecystitis. The experiment was conducted on 60 male rabbits with an ADC model created by ligation of the cystic duct and injection of a bacterial suspension. The animals were divided into 5 groups according to the sampling time point (baseline, 2, 5, 7, 10 days). Markers of lipid peroxidation (LPO) – diene conjugates (DC), ketodienes (KD), malondialdehyde (MDA); activity of the antioxidant system (AOS) – total antioxidant activity (TAA) and catalase; markers of EI – concentration of middle molecular weight peptides (MMWP) and phospholipase A2 activity; as well as the phospholipid composition of erythrocyte membranes were determined in erythrocyte membranes and blood plasma. A progressive activation of LPO was revealed: by day 7, the levels of DC, KD and MDA significantly increased by 2.9, 5.4 and 3.7 times, respectively, compared to the baseline (p<0.001). By day 5, depletion of the AOS was recorded – a decrease in plasma TAA and catalase activity (p<0.05), reaching a maximum by day 7 (a 3-fold decrease, p<0.001). EI increased in parallel: the concentration of MMWP doubled by day 7 (p<0.001), and phospholipase A2 activity increased 5-fold (p<0.001). Strong positive correlations were established between LPO markers, MMWP and phospholipase A2 activity (r=0.63-0.78). The development of experimental destructive cholecystitis is characterized by a staged formation of a vicious cycle initiated by oxidative stress, which leads to depletion of the antioxidant system, activation of phospholipase A2, profound disruption of cell membrane structure, and an increase in endogenous intoxication.