Cargando…

Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells du...

Descripción completa

Detalles Bibliográficos
Autores principales: Drafi, Frantisek, Bauerova, Katarina, Kuncirova, Viera, Ponist, Silvester, Mihalova, Danica, Fedorova, Tatiana, Harmatha, Juraj, Nosal, Radomir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Slovak Toxicology Society SETOX 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485659/
https://www.ncbi.nlm.nih.gov/pubmed/23118593
http://dx.doi.org/10.2478/v10102-012-0015-4
_version_ 1782248333999341568
author Drafi, Frantisek
Bauerova, Katarina
Kuncirova, Viera
Ponist, Silvester
Mihalova, Danica
Fedorova, Tatiana
Harmatha, Juraj
Nosal, Radomir
author_facet Drafi, Frantisek
Bauerova, Katarina
Kuncirova, Viera
Ponist, Silvester
Mihalova, Danica
Fedorova, Tatiana
Harmatha, Juraj
Nosal, Radomir
author_sort Drafi, Frantisek
collection PubMed
description Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe(2+)-induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of methotrexate treatment in rat AA.
format Online
Article
Text
id pubmed-3485659
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Slovak Toxicology Society SETOX
record_format MEDLINE/PubMed
spelling pubmed-34856592012-11-01 Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate Drafi, Frantisek Bauerova, Katarina Kuncirova, Viera Ponist, Silvester Mihalova, Danica Fedorova, Tatiana Harmatha, Juraj Nosal, Radomir Interdiscip Toxicol Original Article Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe(2+)-induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of methotrexate treatment in rat AA. Slovak Toxicology Society SETOX 2012-06 2012-06 /pmc/articles/PMC3485659/ /pubmed/23118593 http://dx.doi.org/10.2478/v10102-012-0015-4 Text en Copyright © 2012 Slovak Toxicology Society SETOX http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Drafi, Frantisek
Bauerova, Katarina
Kuncirova, Viera
Ponist, Silvester
Mihalova, Danica
Fedorova, Tatiana
Harmatha, Juraj
Nosal, Radomir
Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate
title Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate
title_full Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate
title_fullStr Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate
title_full_unstemmed Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate
title_short Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate
title_sort pharmacological influence on processes of adjuvant arthritis: effect of the combination of an antioxidant active substance with methotrexate
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485659/
https://www.ncbi.nlm.nih.gov/pubmed/23118593
http://dx.doi.org/10.2478/v10102-012-0015-4
work_keys_str_mv AT drafifrantisek pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT bauerovakatarina pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT kuncirovaviera pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT ponistsilvester pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT mihalovadanica pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT fedorovatatiana pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT harmathajuraj pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate
AT nosalradomir pharmacologicalinfluenceonprocessesofadjuvantarthritiseffectofthecombinationofanantioxidantactivesubstancewithmethotrexate