Tag Archives: L-arginine
L-arginine, aminoguanidine and mesenchymal stem cells reduce the level of endoplasmic reticulum stress markers and D-dimer in the lungs of mice with antiphospholipid syndrome
N. Ya. Mekhno*, A. I. Dovgalyuk, O. S. Tokarskyy,
M. M. Korda, O. Z. Yaremchuk*
I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine;
*e-mail: mekhno_nyar@tdmu.edu.ua; yaremchuk@tdmu.edu.ua
Received: 22 May 2024; Revised: 20 July 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by damage to the intima of the microcirculatory blood vessels as a result of the formation of autoimmune antibodies to phospholipids of cell membranes. Recent data indicate a possible link between the occurrence of autoimmune diseases and endoplasmic reticulum stress, impaired nitric oxide availability, high plasma D-dimer level. The aim of the study was to estimate the effect of nitric oxide synthesis modulators L-arginine and aminoguanidine, and mesenchymal stem cells on the level of inositol-requiring enzyme-1a (IRE-1a), glucose-regulated protein 78 (GRP-78) as ER stress markers, and the level of D-dimer in the lung tissue of female BALB/c line mice with experimental APS induced with cardiolipin administration. 30 experimental animals were divided into five groups: 1 – control animals; 2 – mice with APS; 3 – mice with APS, injected intraperitoneally with L-arginine hydrochloride (25 mg/kg) and aminoguanidine (10 mg/kg); 4 – mice with APS, injected intraperitoneally with stem cells (5×106/kg); 5 – mice with APS, injected with L-arginine hydrochloride, aminoguanidine and stem cells in combination. After 10 days post APS formation animals were removed from the experiment, proteins were extracted from the lung tissue and their level was determined with Western blotting. It was established that in group with APS the levels of IRE-1, GRP-78 and D-dimer were substantially increased as compared to the control group. After separate administration of both arginine with aminoguanidine and MSC, as well as with their combined use, the level of IRE-1, GRP-78 and D-dimer decreased compared to the indices in animals with induced APS. The obtained data indicated that this effect is probably due to the reduction of ER stress through iNOS inhibition and the anti-inflammatory action of MSCs.
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.
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.