Age-Dependence of Biochemical Manifestations of Hepatotoxicinjury in Rat Exposed to Xenobiotics of Various Genesis

Abstract

Currently, the problem of liver diseases against the backdrop of the toxic effects of medicinal and industrial (herbicides) xenobiotics on the body is becoming increasingly relevant. The activation of compensatory mechanisms in response to the action of toxic agents –acetaminophen and/or diquat is closely related to age-specific features. Heightened focus on acetaminophen-induced injury is linked to the widespread use of this medication as an analgesic and antipyretic during pandemics of infectious and inflammatory diseases, especially under the conditions of warfare in Ukraine. In return, the widespread use of the herbicide diquat is accompanied by an increase in the registration of cases of diquat -induced acute poisoning. The aim of study was to evaluation the biochemical parameters of the functional state of the liver of different-aged rats under conditions of acetaminophen-and diquat-induced toxic injury. Animals were divided into three age groups: adolescent (60 days), reproductive (150 days), and mature age rats (360 days). Acute toxic injury by acetaminophen was modeled by its oral administration through gastric intubation at a daily dose of 1250 mg/kg of the animal's body weight during the last 2 days of the experiment. Acute toxic damage by diquat was modeled by a single intragastric administration using a probe at a dose of 115.5 mg/kg of the animal's body weight. The functional state of the liver was assessed on an automatic biochemical analyzer NTI Biochem FC-120.Acetaminophen intoxication led to an increase in the absolute liver mass indicator, organ index, changes in the macroscopic structure of the organ, increased serum activities of ALT and AST, total LDH, and a decrease in the De Ritis ratio amidst increased activities of ALP, GGT, and levels of total and indirect bilirubin in all age groups compared to the control. The most significant changes were observed in mature age animals (increase in ALT activity by 76%, AST by 56%, ALP by 51%, GGT by 51%, and a decrease in the De Ritis ratio by 47%). Under conditionsof diquat-induced toxic injury, a slightly different trend and degree in manifestation of established changes are observed. A more pronounced hepatotoxic effect was registered in adolescent animals, manifested by the maximum increase in absolute liver mass by 26%, ALT activity by 71%, AST by 47%, ALP by 50%, Bili-T level by 69%. No statistically significant differences compared to the control and APAP-induced injury in the activity of total LDH and GGT upon administration of toxic doses of the herbicide diquat regardless of age category were observed.Based on the experimental results, an age-related multidirectionality in the adverse effects of the medicinal xenobiotic acetaminophen and the industrial xenobiotic diquat on indicators of the morpho-functional state of the liver is observed. The most sensitive age group of animals to toxic injury by acetaminophen are rats of 360 days of age, while for diquat –60 days of age