THE OVERWEIGHT AND OBESITY ROLE IN THE OCCURRENCE OF CHEMOTHERAPY-INDUCED HEPATOTOXIC REACTIONS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA.

OBJECTIVE: The aim: To investigate the frequency of development and nature of cytostatic-induced hepatotoxic reactions in patients with acute myeloid leukemia (AML) with overweight and obesity during remission induction сhemotherapy (CT). PATIENTS AND METHODS: Materials and methods: We examined 25 patients with newly diagnosed acute leukemia (AL), of which 56% (14/25) were men, 44% (11/25) were women. Depending on the body mass index (BMI), patients were divided into groups: I (n=10) - patients with AML and BMI of 18.5-24.9 kg/m2; IІ (n=15) - patients with AML and BMI ≥25.0 kg/m2. The biochemical blood analysis was evaluated twice: before and on the 56th day of CT, which included alanine-, aspartate-aminotransferases, gamma-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), total protein and total bilirubin. RESULTS: Results: In patients with AML and normal BMI, CT conduction increased the risk of GGT (RR=3.00; 95% CI=1.14-7.91; p<0.05) and ALP activity impairment (RR=2.67; 95% CI=0.98-7.22; p>0.05). The presence of overweight and obesity in patients with AML of group II led to significant risk of increase the GGT (RR=3.00; 95% CI=1.46-6.14; p<0.05) and ALP activity (RR=4.00; 95% CI=1.41-11.35; p<0.05) during CT. GGT and ALP activity in the blood serum of group II patients after CT exceeded the baseline data in 2.4 times (p<0.0001) and 1.6 times (p=0.0007), respectively. CONCLUSION: Conclusions: The remission induction CT of AML is accompanied by the risk of cytostatic-induced liver injury. The presence of overweight, obesity and primary disorders of biochemical liver tests due to the oncohematological disease influence are the risk factors for hepatotoxic reactions development during CT.

THE EFFECT OF S-ADEMETIONINE ON PLASMA CITRULLINE LEVEL DURING CHEMOTHERAPY-INDUCED OXIDATIVE STRESS IN PATIENTS WITH CHRONIC LYMPHOPROLIFERATIVE DISORDERS.

OBJECTIVE: The aim: To investigate the effect of S-ademetionine on plasma citrulline level in patients with chronic lymphoproliferative disorders (CLPD) during chemotherapy-induced oxidative stress. PATIENTS AND METHODS: Materials and methods: 25 patients with CLPD were examined. Examinations were conducted twice: before chemotherapy (CT) and after 3 courses of CT. Several biochemical markers in the blood were determined: the activity of catalase, the level of plasma citrulline, the concentration of N-acetylneuraminic acid (NANA) and the concentration of substances that form a trimethine complex (TBARS) with 2-thiobarbituric acid. Patients were divided into groups: І (n=14) - patients who underwent only CT; ІІ (n=16) - patients who during CT received S-ademetionine, at a dose of 1000 mg/day intravenously for 10 days, then 500 mg twice a day for 20 days. ІІІ (n=20) -the control group of 20 practically healthy individuals. RESULTS: Results: Patients in both groups with CLPD had pre-existed mucosal injury that was characterized by 1.25 (p=0.0025) and 1.26 times (р=0.006) higher blood NANA concentration compared to the control group. The conduction of CT was associated with enterocytes dysfunction, which was characterized by 1,66 times (p=0,0002) lower plasma citrulline level in patients of group I compared to the initial examination. The infusion of S-ademetionine attenuated intestinal dysfunction that was associated with 1,23 times (p=0,0005) higher blood citrulline level after the CT as compared to group I. CONCLUSION: Conclusions: The infusion of S-ademetionine as adjuvant treatment in patients with CLPD provided effective prophylaxis of intestinal injury that was associated with higher blood citrulline level after the conduction of CT.

THE EFFECT OF DOXORUBICIN-INDUCED OXIDATIVE STRESS ON CITRULLINE CONCENTRATION IN THE SMALL INTESTINAL MUCOSA AND PLASMA BLOOD IN RATS WITH NON-ALCOHOLIC STEATOHEPATITIS.

OBJECTIVE: 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). PATIENTS AND METHODS: 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: 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. CONCLUSION: 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.

Arginine/citrulline cycle changes in diet-induced rat model of non-alcoholic fatty liver disease.

OBJECTIVE: The aim: to study the Arginine / Citrulline-cycle features on a diet-induced rat model of non-alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: Materials and methods: The studies were carried out on 20 white non-linear adult rats, including 10 (50%) males, 10 (50%) females, weighing 160-220 g. NAFLD was modeled by a 9-week fast food diet. The level of arginine and citrulline, and the arginase activity were investigated in the animals' liver homogenates and in the blood. The morphological analysis of liver tissues changes was done. RESULTS: Results: NAFLD modeling using a 9-week fast food diet resulted in maximum weight gain in male rats (р<0.05). Female rats had 3 times more accumulation of intra-abdominal fat than male rats in the main group (р<0.05). Histopathologic liver examination confirmed NAFLD development in rats on a fast food diet during 9 weeks (р<0.05). NAFLD led to an increment of arginine level in the blood and liver homogenate in the main group compared to controls (р<0.05). NAFLD development was accompanied by a decrease in arginase activity and citrulline level in the blood and liver homogenate compared to control (р<0.05). CONCLUSION: Conclusions: The experimental rat model of NAFLD showed the Arginine / Citrulline cycle disorders, that were characterized by an increased arginine level, a decreased arginase activity and citrulline concentration in the blood and liver tissues.