Abstract
Against the manifest of acute myeloid leukemia (AML) in patients with concomitant obesity there is a high risk of liver injury development, that requires a detailed study of its pathogenesis. The aim - to investigate the effect of Arginine/Citrulline cycle disorders on the liver injury development in obese AML patients. We examined 20 patients with newly diagnosed AML, including 10 (50%) men and 10 (50%) women, aged 18-77 years. The body mass index (BMI) was calculated. The study included AML patients with BMI above 25. The average BMI was 29.35±0.93 kg/m2. The biochemical blood test was assessed (alanine and asparagine (AST) aminotransferases, total bilirubin, alkaline phosphatase (AP), gammaglutamyltranspeptidase (GGTP), urea). Arginase, ornithine decarboxylase (ODC) activity, arginine and citrulline content were measured in the blood serum before induction chemotherapy. Viral hepatitis B and C were excluded. Statistical analysis was performed. In AML patients with concomitant obesity before chemotherapy AST was 1.7-fold higher (p=0.03), AP – 1.7-fold (p=0.002), GGTP – 2.4-fold (p=0.001), the content of total bilirubin – 1.8-fold (p=0.002) and urea - 2.9-fold (p=0.0003) higher than normal ranges. The study results showed a 3-fold decrease in arginine content (p<0.0001) compared to normal. At the same time there was an increase in arginase activity in 3.9 times (p<0.0001), ODC – in 1.9 times (p=0.0007), citrulline content – in 7.6 times (p=0.0001) compared with control. There was a strong inverse correlation between the concentration of citrulline and ODC activity in the blood serum of obese AML patients (r=-0.61; p<0.05), a moderate direct correlation between the ODC activity and AP in these patients was also revealed (r=+0.44; р<0.05). Consequently, the liver injury with cytolytic and cholestatic syndromes in AML patients with concomitant obesity may be caused by the disorders in the Arginine/Citrulline cycle, which were associated with an increased ODC activity in the blood serum. Excess weight and obesity affect serum arginine level, leading to potential drug-induced hepatotoxicity development during induction chemotherapy.
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