Tag Archives: L-arginine

Indexes of nitric oxide system in experimental antiphospholipid syndrome

O. Z. Yaremchuk, K. A. Posokhova, І. P. Kuzmak,
M. I. Kulitska, I. М. Klishch, M. M. Korda

I. Horbachevsky Ternopil National Medical University, Ukraine;
e-mail: yaremchuk@tdmu.edu.ua

Received: 11 November 2019; Accepted: 21 January 2020

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antibo­dies to negatively charged membrane phospholipids (aPL).  Endothelial dysfunction is one of the most dangerous­ APS manifestations followed by thrombosis, placental insufficiency and often foetal death due to circulatory disorders in placenta blood vessels. It is established that synthesis and bioavailability of nitric oxide (NO) in the endothelium are impaired at APS, but the role of NO system in pregnancy failure at this pathology remains ambiguous. The aim of this research was to estimate the indexes of the nitric oxide system in animals with an experimental antiphospholipid syndrome before pregnancy and on the 18th day of pregnancy, without­ treatment and under treatment with nitric oxide synthesis modulators (L-arginine and aminoguanidine). In the blood serum and liver of the BALB/c mice with experimental APS, the content of eNOS and iNOS by ELISA and the level of NO2 and NO3 with the use of Gris reagent were determined before pregnancy and on the 18th day of pregnancy. The data obtained indicate the relative inefficient NO production by eNOS and NO hyperproduction by iNOS in the blood serum and liver of mice in the pathogenesis of experimental APS. Thus, in mice with APS before pregnancy and on the 18th day of the pregnancy, the eNOS content and NO2 level were decreased while the iNOS content and NO3 level were increased compared to the indexes in the control animal group. L-arginine administration to the animals with APS at the follow-up periods resulted in an increased eNOS content and NO2, NO3 levels in blood serum and liver with the simultaneous decrease in iNOS content in the liver as compared to indexes in untreated mice with APS. The combined use of L-arginine and selective iNOS inhibitor aminoguanidine caused a significant increase in eNOS content and a decrease in iNOS content followed by normalization of NO2 and NO3 levels in blood and liver of mice with  experimental APS before pregnancy and on the 18th day of pregnancy compared to untreated mice with APS.

The liver and kidneys biochemical indices at the experimental pancreatitis in case of the administration of nitric oxide synthesis modulators and recombinant superoxide dismutase

O. Z. Yaremchuk, K. A. Posokhova

SHEI «I. Ya. Horbachevsky Ternopil State Medical University», Ukraine;
e-mail: yaremchukolya@rambler.ru

The rats liver and kidneys function indices were studied in case of administration of recombinant superoxide dismutase drug, precursor of nitric oxide L-arginine and the blocker of inducible NO-synthase aminoguanidine. The disturbances in functioning of prooxidant-antioxidant system (a decrease of activity of superoxide dismutase, katalaze, amount of restored glutathione, growth of the level of hydroperoxide lipids, TBA-active products­), mitochondrial electron-transport pathways (a decrease in activity of succinatedehydrogenaze, cytochrome oxydaze), a rise of nitrite-anion level in the liver and kidneys, increase of α-amylase activity and tumor necrosis factor α serum concentration were established on the model of pancreas injury in white male rats. Under these circumstances aminoguanidine attenuated the oxidative stress in the liver and kidneys due to normalization of nitric oxide synthesis. The ability to activate the antioxidant system was proved by combined usage of recombinant superoxide dismutase and aminoguanidine. It was determined that recombinant superoxide dismutase partially decreases the negative influence of L-arginine and improves the biochemical indices of the liver and kidneys function in rats with acute experimental pancreatitis.

Rat liver arginase system under acetaminophen-induced toxic injury and protein deprivation

H. P. Kopylchuk, I. M. Nykolaichuk, O. M. Zhuretska

Yuriy Fedkovych Chernivtsi National University, Ukraine;
Institute of Biology, Chemistry and Bioresourses, Chernivtsi, Ukraine;
e-mail: kopilchuk@gmail.com

Arginase activity and L-arginine content in both cytosolic and mitochondrial fractions of rat liver cells under the conditions of toxic injury on the background of protein deprivation was studied. The most significant reduction of arginase activity in liver cells and depletion of L-arginine pool was found in rats with toxic acetaminophen-induced liver injury maintained on the ration balanced by all nutrients as well as in protein deficiency rats. It was concluded that reduction of the arginase activity in the cytosolic fraction of rat liver cells, combined with simultaneous decrease of L-arginine content, may be considered as one of the mechanisms of ornithine cycle disturbance. The decline of activity of mitochondrial isoform of arginase II, for certain, is related with activation of NO-synthase system.

Peculiarities of arginase and NO-synthase pathways of L-arginine metabolism in peripheral blood lymphocytes of patients with ovarian cancer

O. I. Yakubets, R. V. Fafula, D. Z. Vorobets, Z. D. Vorobets

Danylo Halytski Lviv National Medical University, Ukraine;
е-mail: vorobets@meduniv.lviv.ua

The peculiarities of arginase and NO-synthase pathways of L-arginine metabolism in peripheral blood lymphocytes of patients with ovarian cancer were studied. It was shown that the development of cancer pathology is associated with an imbalance in the NO synthesis in blood lymphocytes. The reason for such imbalance is the activation of arginase and inducible isoform of NO-synthase (iNOS) and significant inhibition of its constitutive isoform. The analysis of the kinetic properties of NOS of blood lymphocytes of patients with ovarian cancer was carried out. It was shown that the affinity constant of iNOS affinity for L-arginine is 5.4-fold lower than for eNOS of blood lymphocytes of persons in the control group. The inhibition of eNOS occurs via non-competitive type and is related to the reduction of maximum reaction rate.