PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF). An animal CRF model was produced in rats by a two-stage operative res...

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Autores principales: M. V. Osikov, O. A. Gizinger, D. A. Cherepanov
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Lenguaje:RU
Publicado: SPb RAACI 2016
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spelling oai:doaj.org-article:1443b1e83a28411e9c3e3e558d4c34332021-11-18T08:03:45ZPATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE1563-06252313-741X10.15789/1563-0625-2016-3-231-2https://doaj.org/article/1443b1e83a28411e9c3e3e558d4c34332016-07-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1035https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThe purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF). An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes), CD45RA+ (mainly, B cells), as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis), Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells). Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH), IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD) and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma. Amlodipine administration lead to restoration of Th1 and Th2 dependent immune response, increased number of cells positive for T and B lymphocyte markers. Probable immune mechanisms of amlodipine effects may be associated with decreased numbers of apoptotic/necrotic lymphocytes, reduced lipid peroxidation in peripheral blood lymphocytes, enhanced SOD activity in blood plasma.M. V. OsikovO. A. GizingerD. A. CherepanovSPb RAACIarticleamlodipineimmune statecytokineslymphocytesapoptosisfree radical oxidationchronic renal failureImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 18, Iss 3, Pp 231-2 (2016)
institution DOAJ
collection DOAJ
language RU
topic amlodipine
immune state
cytokines
lymphocytes
apoptosis
free radical oxidation
chronic renal failure
Immunologic diseases. Allergy
RC581-607
spellingShingle amlodipine
immune state
cytokines
lymphocytes
apoptosis
free radical oxidation
chronic renal failure
Immunologic diseases. Allergy
RC581-607
M. V. Osikov
O. A. Gizinger
D. A. Cherepanov
PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE
description The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF). An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes), CD45RA+ (mainly, B cells), as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis), Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells). Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH), IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD) and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma. Amlodipine administration lead to restoration of Th1 and Th2 dependent immune response, increased number of cells positive for T and B lymphocyte markers. Probable immune mechanisms of amlodipine effects may be associated with decreased numbers of apoptotic/necrotic lymphocytes, reduced lipid peroxidation in peripheral blood lymphocytes, enhanced SOD activity in blood plasma.
format article
author M. V. Osikov
O. A. Gizinger
D. A. Cherepanov
author_facet M. V. Osikov
O. A. Gizinger
D. A. Cherepanov
author_sort M. V. Osikov
title PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE
title_short PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE
title_full PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE
title_fullStr PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE
title_full_unstemmed PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE
title_sort pathogenesis of immune alterations and corrective role of amlodipine in experimental chronic renal failure
publisher SPb RAACI
publishDate 2016
url https://doaj.org/article/1443b1e83a28411e9c3e3e558d4c3433
work_keys_str_mv AT mvosikov pathogenesisofimmunealterationsandcorrectiveroleofamlodipineinexperimentalchronicrenalfailure
AT oagizinger pathogenesisofimmunealterationsandcorrectiveroleofamlodipineinexperimentalchronicrenalfailure
AT dacherepanov pathogenesisofimmunealterationsandcorrectiveroleofamlodipineinexperimentalchronicrenalfailure
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