Вплив комбінації L-аргініну та L-карнітину на прооксидантно- антиоксидантний статус і аргінін-цитруліновий цикл у хворих на множинну мієлому із супутньою ішемічною хворобою серця в динаміці хіміотерапії

Abstract

Мета — дослідити вплив комбінації L-aргініну та L-карнітину на прооксидантно-антиоксидантний статус та аргінін-цитруліновий цикл у хворих на множинну мієлому (ММ) із супутньою ішемічною хворобою серця (ІХС) у динаміці хіміотерапії. Матеріали та методи. Обстежено 59 пацієнтів із прогресуванням ММ та супутньою ІХС. Пацієнти були розподілені на групи залежно від наявності супутньої ІХС та призначених лікувальних комплексів: I (n = 20) — хворі на ММ без супутніх захворювань серцево-судинної системи, які отримували стандартну хіміотерапію, IІ (n = 22) — хворі на ММ із супутньою ІХС, які отримували стандартну хіміотерапію та базисну медикаментозну терапію ІХС, ІІІ (n = 17) — хворі на ММ із супутньою ІХС, які отримували стандартну хіміотерапію, стандартну медикаментозну терапію ІХС у комбінації з L-аргініном та L-карнітином. Усім хворим призначали бортезомібвмісні схеми хіміотерапії. Пацієнти були обстежені до початку хіміотерапії та перед п’ятим курсом хіміотерапії. Визначали концентрацію L-aргініну, цитруліну, реактантів тіобарбітурової кислоти (ТБК), активність аргінази й каталази в сироватці крові.

Objective — to investigate the influence of the combination of L-arginine and L-carnitine on prooxidant-antioxidant status and arginine-citrulline cycle in patients with multiple myeloma (MM) and concomitant coronary artery disease (CAD) during the chemotherapy. Materials and methods. 59 patients with multiple myeloma progression and concomitant coronary artery disease were examined. According to the presence of concomitant coronary artery disease and prescribed treatment, all patients were divided into groups: I (n = 20) — patients with multiple myeloma and no concomitant diseases of the cardiovascular system, who received the standard chemotherapy, II (n = 22) — patients with multiple myeloma and concomitant coronary artery disease, who received standard chemotherapy and basic treatment of coronary artery disease, III (n = 17) — patients with multiple myeloma and concomitant coronary artery disease who received standard chemotherapy, basic treatment of coronary artery disease in combination with L-arginine and L-carnitine. All patients obtained bortezomib-containing schemes of chemotherapy. Patients were examined twice: before the initiation of chemotherapy and before the fifth course of chemotherapy. The concentration of L-arginine, citrulline, thiobarbituric acid reactants (TBAR), and the activity of arginase and catalase in blood serum were measured. Results. During the multiple myeloma progression in patients of groups II and III, the concentration of TBAR-substances was increased by 1.3 times (р < 0.0001) compared with patients of group I. Simultaneously, in patients of groups II and III, the catalase activity decreased by 1.3 times (р < 0.0001), and the concentration of serum citrulline was 1.7 times (р < 0.0001) and 1.9 times (р < 0.0001) higher than in patients of group I. Before the fifth course of chemotherapy in patients of group III, the concentration of serum L-arginine was 1.1 times ((71.11 (68.74; 77.79) vs. 64.25 (59.41; 69.47)) μmol/l, р = 0.0001) higher than in patients of group II. Simultaneously, the concentration of serum citrulline was increased by 1.3 times ((250.5 (205.4; 285.3) vs. 197.0 (175.0; 243.5)) μmol/l. р = 0.007) compared with group II. In patients of groups I and III the activity of catalase in blood serum was increased by 1.1 times ((13.77 (12.50; 14.86) vs. 15.37 (14.24; 16.01)) μkat/l. р < 0.05) and by 1.4 times ((10.43 (9.55; 10.75) vs. 14.26 (12.45; 15.81)) μkat/l, р < 0.001), respectively, compared with the initial examination. However, in patients of group II, it was decreased by 1.3 times ((10.07 (9.40; 10.25) vs. 8.00 (7.74; 8.23)) μkat/l. р < 0.001) compared to the initial examination. Multiple myeloma progression was accompanied by prooxidant-antioxidant status disorders, which were represented by increasing concentrations of TBAR-substances independent from the presence of concomitant coronary artery disease. However, in patients with multiple myeloma and concomitant coronary artery disease, serum concentration of TBAR-substances was significantly higher compared with patients with multiple myeloma without concomitant diseases of the cardiovascular system. According to our study, the administration of L-arginine and L-carnitine significantly increases the concentration of L-arginine in the blood serum, which decreases the level of endothelial dysfunction by the augmentation of nitric oxide production in the background of reduced oxidative stress and arginase activity. Conclusions. Addition of L-arginine and L-carnitine to the supportive therapy of patients with multiple myeloma with concomitant coronary artery disease leads to a significant decrease of TBAR-substances concentration in the blood serum with simultaneous augmentation of catalase activity in the blood serum (р < 0.05) during the chemotherapy, which makes these indicators equivalent to those of patients with multiple myeloma without concomitant disease of the cardiovascular system (р > 0.05). L-arginine and L-carnitine significantly increase the concentration of L-arginine in the blood serum of patients with multiple myeloma and concomitant coronary artery disease during the chemotherapy (р > 0.05), which contributes to the decreasing of oxidative stress severity and improvement of endothelial function by efficient NOSdependent L-arginine unitization with NO formation.