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...
Autores principales: | , , , , , , , |
---|---|
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 |