Tag Archives: arginase

The level of nitric oxide and arginase activity in patients with arterial hypertension and diabetes mellitus during COVID-19

O. Y. Sklyarova1, S. R. Mahiiovych2, N. V. Denysenko3,
L. I. Kobylinska3*, Y. Y. Sklyarov2

1Department of Family Medicine FPGE, Danylo Halytsky Lviv National Medical University, Ukraine;
2Department of Therapy No 1 and Medical Diagnostics FPGE, Danylo Halytsky Lviv National Medical University, Ukraine;
3Department of Biological Chemistry, Danylo Halytsky Lviv National Medical University, Ukraine;
*e-mail: lesyaivanivna.biochemistry@gmail.com

Received: 28 September 2022; Revised: 06 November 2022;
Accepted: 11 November 2022; Available on-line: 19 December 2022

The aim of this study was to assess the level of nitric oxide production and arginase activity in patients with arterial hypertension and type II diabetes mellitus during infection with SARS-CoV-2. The study groups included patients with arterial hypertension, patients with arterial hypertension combined with a severe course of COVID-19 and patients who, in addition to arterial hypertension and COVID-19, were suffering from type II diabetes mellitus. The volunteers without any clinical signs of diseases and normal blood pressure formed the control group. It has been established that arterial hypertension, combined with COVID-19 occurs along with reduced L-arginine, nitric oxide, superoxide dismutase activity and increased arginase activity. At the same time, the presence of arterial hypertension in patients with diabetes and coronavirus disease is accompanied by a decline in the content of L-arginine and arginase activity. Our study’s results may help scientists find new pharmacological targets in the future treatment of coronavirus disease and comorbid disorders.

The effect of thymic mesenchymal stromal cells on arginase activity and nitric oxide produced by mouse macrophages

R. S. Dovgiy1,2, I. S. Nikolsky3, L. M. Skivka1

1Taras Shevchenko National University of Kyiv, Ukraine;
2Institute of Gerontology, NAMS of Ukraine, Kyiv;
3State Institute of Genetic and Regenerative
Medicine NAMS of Ukraine, Kyiv;
e-mail: romandovgiy@gmail.com

Mesenchymal stromal cells (MSC) gained much attention due to their therapeutic properties, media­ted largely by anti-inflammatory action. We aimed to investigate the capacity of MSC obtained from young mice to modulate arginine metabolism of macrophages from old animals. Bone marrow cells obtained from young and aged mice were cocultivated with MSC in the presence of M-CSF. Nitric oxide production was analyzed in supernatants by Griess reaction, and arginase activity was measured in cell lysates. We have found that arginase activity was significantly lower in macrophages isolated from old mice as compared to young animals (P ˂ 0.05). Syngeneic MSC addition markedly stimulated arginase activity in macrophages from both young and aged mice (P ˂ 0.001), with greater effect in old animals. There were no significant differences in nitric oxide level between groups. In summary, there was more pronounced anti-inflammatory shift in macrophage metabolism in aged animals upon cocultivation with MSC.

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.

Effects of the combined arginase and canavanine treatment on leukemic cells in vitro and in vivo

O. I. Vovk1, O. I. Chen1,2, N. I. Igumentseva1, O. Yu. Senchuk1,
M. L. Barska1, N. O. Sybirna1,2, O. V. Stasyk1

 1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Ivan Franko National University of Lviv, Ukraine;
e-mail: stasyk@cellbiol.lviv.ua

It was previously demonstrated in in vitro experiments that canavanine (Cav), a natural toxic arginine analogue of plant origin, is a promising candidate for augmenting the antineoplastic effects of arginine starvation. We demonstrated herein that recombinant human arginase, an arginine degrading enzyme, abrogated growth and significantly increased Cav cytotoxicity toward cultured L1210 murine leukemic cells. Cav co-treatment further reduced cells viability in a time-dependent manner and significantly promoted apoptosis induction. In the pilot study we also evaluated for the first time the potential toxicity of the combined arginine deprivation and Cav treatment in healthy mice. Administration of Cav alone or in combination with pegylated cobalt-containing human arginase (Co-hARG) did not evoke any apparent toxic effects in these animals, with no significant behavioural and survival changes after several weeks of the treatment. The therapeutic effects of the combination of Co-hARG and Cav were provisionally evaluated on the highly aggressive murine L1210 leukemia, which is semi-sensitive to arginine deprivation as a monotreatment. Combination of two drugs did not result in significant prolongation of the survival of leukemia-bearing mice. Thus, we have shown that the proposed combinational treatment is rather non-toxic for the animals. It has to be further evaluated in animal studies with alternative tumor models and/or drug doses and treatment modalities.

The effect of agmatine on L-arginine metabolism in erythrocytes under streptozotocin-induced diabetes in rats

I. V. Ferents, I. V. Brodyak, M. Ya. Lyuta,
V. A. Burda, A. M. Fedorovych, N. O. Sybirna

Ivan Franko National University of Lviv, Ukraine;
e-mail: sybirna_natalia@yahoo.com

The effects of agmatine on oxidative and non-oxidative metabolic pathways of L-arginine were investigated both in plasma and erythrocytes under experimental diabetes mellitus. It was indicated, that agmatine prevents the development of oxidative-nitrosative stress in diabetic rats. After treatment of animals by agmatine NO-synthase methabolic pathway of L-arginine is depressed whereas arginase one increases in erythrocytes of rats with experimental diabetes mellitus.

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.