Effect of L-arginine and aminoguanidine on the cytokine profile in obstetric antiphospholipid syndrome

Yaremchuk, O. Z.; Посохова, К. А.; Lykhatskyi, P. H.; Letniak, N. Ya.; Moseychuk, I. P.

doi:10.15421/022018

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…L-arginine decreases IL-1β and others proinflamatory cytokine, potentially reducing apoptosis and cellular senescence [23]. Data about reduction of proinflammatory cytokines in the lung tissue of mice with APS were used combination of L-arginine and aminoguanidine are in accordance with the data of Yaremchuk and others [13] regarding the reduction of cytokines in the serum of BALB/c mice with APS on the 18th day of pregnancy.…”

Section: Fig 1 Il-1β Level In Bronchoalveolar Lavage In Mice With Ant...supporting

confidence: 62%

“…NO regulates several physiological processes, including thrombosis, endothelial-leukocyte interactions, vascular cell migration and proliferation, as well as modulation of vascular tone and permeability. In norm, NO is synthesized in the vascular wall owing to the endothelial isoform of NO synthase (eNOS) [11,12,13]. The role of NO in the pathogenesis of APS is associated with both direct and indirect action.…”

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confidence: 99%

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Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice

Mekhno,

Dovgalyuk,

Korda

et al. 2024

COT

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Antiphospholipid syndrome is an autoimmune disease characterized by vascular thrombosis and/or obstetric pathology and the presence of antibodies against membrane phospholipids or certain phospholipid-related proteins. Objective. The aim of the research is to study the effect of mesenchymal stem cells, nitric oxide modulators (L-arginine and aminoguanidine) on the level of cytokines in bronchoalveolar lavage in experimental antiphospholipid syndrome in mice. Material and methods. Antiphospholipid syndrome was modeled on female BALB/c mice by intramuscular injections of cardiolipin 1.2 mg/kg 4 times with a 14-day interval. Cryopreserved human umbilical cord-derived mesenchymal stem cells (5×106 cells/kg) were injected once intraperitoneally, L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were administered intraperitoneally 1 time per day during 10 days after APS had developed. The cytokines concentration in bronchoalveolar lavage from the lungs was assessed by means of ELISA in 10 days after APS development. Results. In the bronchoalveolar lavage of the BALB/c mice with experimental APS, an increased level of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and decreased level of anti-inflammatory IL-4 and IL-10 were found. It was established that in cases of APS and administration of stem cells the concentration of proinflammatory cytokines decreased: IL-1β by 32.4 %, IL-6 by 30.6 % and TNF-α by 36.1 %, respectively, compare to the APS animals. At the same time the level of IL-4 increased by 50.5 % and IL-10 – by 57.5 % in the group of animals administered with stem cells compare to those with APS. Conclusion. In cases of correction of modeled antiphospholipid syndrome in mice using mesenchymal stem cells and combined application of mesenchymal stem cells and nitric oxide modulators (L-arginine and aminoguanidine), a decrease in the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α ) and an increase in the level of anti-inflammatory cytokines (IL-4 and IL-10) in bronchoalveolar lavage has been established.

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Section: Fig 1 Il-1β Level In Bronchoalveolar Lavage In Mice With Ant...supporting

confidence: 62%

mentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice

Mekhno,

Dovgalyuk,

Korda

et al. 2024

COT

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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

Mekhno,

Dovgalyuk,

Tokarskyy

et al. 2024

Ukr.Biochem.J.

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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. Keywords: aminoguanidine, antiphospholipid syndrome, D-dimer, endoplasmic reticulume stress, GRP-78, IRE-1, L-arginine, lung, mesenchymal stem cells

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Impact of modulators of nitric oxide synthesis on the level of cytokines in bronchoalveolar lavage in experimental antiphospholipid syndrome

Mekhno,

Hlyvka,

Furka

et al. 2024

Polski Merkuriusz Lekarski

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Aim: The aim of the research is to study the cytokine prof i le (IL-1β, IL 6, TNF-α, IL-4, IL-10) in bronchoalveolar lavage of lungs in experimental APS and its correction with L-arginine and aminoguanidine. Materials and Methods: Antiphospholipid syndrome was modeled on white female BALB/c mice. L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used for its correction. The concentration of cytokines in bronchoalveolar lavage from the lungs was assessed using the ELISA test. Results: It was established that in cases of APS the concentration of proinf l ammatory cytokines IL-1β, IL-6 and TNF-a increased in 1.9, 2.3 and 6.6 times, respectively, compare to the control. At the same time a decrease of the IL-4 in 1.7 and IL-10 in 1.8 times was found in the APS group compare to the control. L-arginine reduced the level of proinf l ammatory cytokines IL-1β by 22%, IL-6 – by 36%, and TNF-α – by 23% compare to the animals with APS. At the same time, the level of anti-inf l ammatory cytokines increased: IL-4 – by 46%, IL-10 – by 57% compare to the APS animal group. Aminoguanidine, a selective iNOS inhibitor, did not cause any signif i cant decrease in pro-inf l ammatory cytokines but the level of anti-inf l ammatory cytokines IL-4 increased by 44% and IL-10 – by 49%. Conclusions: The precursor of the NO synthesis L-arginine leads to a decrease in the concentrations of IL-1β, IL-6, TNF-a and an increase of IL-4 and IL-10 compare to the group of BALB/c mice with APS.

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Effect of L-arginine and aminoguanidine on the cytokine profile in obstetric antiphospholipid syndrome

Cited by 3 publications

References 13 publications

Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice

Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice

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

Impact of modulators of nitric oxide synthesis on the level of cytokines in bronchoalveolar lavage in experimental antiphospholipid syndrome

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