S-ADEMETHIONINE EFFECT ON THE ACTIVITY OF FREE RADICAL OXIDATION PROCESSES AND ARGININE/CITRULLINE CYCLE WITH DOXORUBICIN-INDUCED LIVER INJURY

Abstract

Seeking for effective methods for doxorubicin-induced toxicity prevention is of great clinical importance. The aim of the study is to investigate the effect of S-ademethionine on the activity of free radical oxidation and antioxidant protection and arginine / citrulline cycle, and the relationship between the indicators during the modeled doxorubicin-induced liver injury in rats. Materials and methods. The series of study were performed on 30 white non-linear adult rats, 15 (50%) males, 15 (50%) females, weighing 160-220 g. The experimental animals were divided into 3 groups: I group (n=10) included rats (5 males and 5 females), which during 3 days were intraperitoneally administered with doxorubicin of 5 mg/kg/day to achieve cumulative dose of 15 mg/kg and 0.9% sodium chloride solution 1 ml; ІІ group (n=10) included rats (5 males and 5 females), which for 3 days were administered with doxorubicin in dosage similar to that in group I and S-ademethionine intraperitoneally in a dose of 100 mg/kg/day with a total dose of 300 mg/kg; ІІІ group (n=10) included rats (5 males and 5 females), which were injected intraperitoneally for 3 days with 0.9% sodium chloride 1 ml solution by 2 injections. Thiobarbituric acid reactants, arginine, catalase, arginase and ornithine decarboxylase activity were studied in the liver homogenate. Results. The rats of group I in the course of doxorubicin administration demonstrated the growth of the thiobarbituric acid reactants in 2.57 times (p=0.002) in the liver homogenate that was accompanied by 1.7-fold decreased arginase activity compared to the control group III. An inverse correlation was found between the content of thiobarbituric acid reactants and arginase activity in the liver homogenate of group I rats (r=-0.71; p=0.02). Coadministration of S-ademethionine and doxorubicin administration led to 1.4-fold increase in catalase activity in the liver homogenate of rats compared to the control (p=0.009) that reduced the severity of oxidative stress and prevented changes in the arginine/citrulline cycle. Conclusions: S-ademethionine combined with doxorubicin, reduces the activity of free radical oxidation by potentiating the production of antioxidant protective enzymes that prevent impairments in the arginine / citrulline cycle.