The effect of doxorubicin-induced oxidative stress on citrulline concentration in the small intestinal mucosa and plasma blood in rats with non-alcoholic steatohepatitis

Abstract

The aim: Is to investigate the effect of doxorubicin-induced oxidative stress on plasma citrulline and citrulline concentration in the small intestinal (SI) mucosa of rats with non-alcoholic steatohepatitis (NASH). Materials and methods: The studies were carried out on 30 white non-linear adult rats, 15 (50%) males, 15 (50%) females, weighing 160-220 g. The rats were divided into three groups: І (n=10) – rats without NASH, received a standard diet, subsequently were injected with doxorubicin in cumulative dose of 15 mg/kg; ІI (n=10) – rats with NASH, received a high-calorie diet with doxorubicin injection similarly to group I; ІІІ (n=10) –control group, received a standard diet, were injected with placebo. In the SI mucosa, the levels of thiobarbituric acid reactive substances (TBARS), citrulline and catalase were determined. Also the level of plasma citrulline was analyzed. Results: Doxorubicin injection resulted in induction of oxidative stress in rats of group I and II, which was characterized by 2.1 (p=0.002) and 1.4 times (р=0.0059) increase in TBARS and in 3.4 (р=0.002), and 5.2 times (р=0.002) decrease in catalase activity respectively comparing with the control group. Simultaneously plasma citrulline level in group I and II was in 1.4 (р=0.0039) and 1,5 times (р=0.0039) respectively lower, compared to the control group. Conclusions: Doxorubicin-induced SI injury was associated with a significant decrease in plasma citrulline in rats regardless of NASH. The plasma citrulline could become an important marker in the assessment of the SI injury in clinical practice.