Doxorubicin-induced arginine/citrulline cycle changes in rat model of non-alcoholic steatohepatitis

Abstract

Introduction: Doxorubicin (Dox) belongs to the group of anthracycline antibiotics, which are widely used in oncological diseases treatment. The high risk of toxic effects is the basis for studying of the main mechanisms of organs and systems Dox-induced injury development. The aim - to investigate the peculiarities of Dox-induced arginine/citrulline cycle changes in rats with simulated non-alcoholic steatohepatitis (NASH). Methods: The studies were conducted on 30 white non-linear adult rats, weighing 160-220 g. The rats were divided into 3 groups: | (n = 10) - rats (5 males, 5 females), on which NASH was modeled during 63 days, then from the 64th till 66th day they were injected with 1 ml of 0.9% sodium chloride solution intraperitoneally; | (n = 10) - rats (S males, 5 females), on which NASH was modeled during 63 days, continued with Dox injections intraperitoneally 5 mg/kg/day from the 64th till the 66th day; Ill (n = 10) - rats (5 males, 5 females), which received a standard vivarium diet during 63 days, from the 64th to 66th day - 1 ml injections of 0,9% sodium chloride solution intraperitoneally. NASH modeling was hold using a diet containing a 42.8% fats mixture and a 4% fructose aqueous solution. On the 67th day, animals were euthanized under thiopental anesthesia at a dose of 50 mg/kg. A 10% liver homogenate was prepared, in which the concentration of arginine, citrulline, and arginase activity were determined.