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Reduction of oxidative stress in adjuvant arthritis. Comparison of efficacy of two pyridoindoles: stobadine dipalmitate and SMe1.2HCl

100%

Ponist S., Mihalova D., Jancinova V., Snirc V., Ondrejickova O., Mascia C., Poli G., Stancikova M., Nosal R., Bauerová K.

2010

vol. 57

issue 2

223-228

The aim of this study was to evaluate the therapeutic potential of oxidative stress (OS) reduction by using pyridoindole (PI) antioxidants in adjuvant arthritis (AA). The substances tested were stobadine dipalmitate (STB) and SMe1. AA was used as animal model. The experiments included healthy animals, control arthritic animals and arthritic animals with administration of PI in the oral daily dose of 15 mg/kg b.m during 28 experimental days. The rats were sacrificed on day 28. Clinical and biochemical parameters were determined. The effect of PI administration was evaluated on the basis of the following parameters: (a) arthritis (volume of hind paws - HPW, change of animal body mass - CBM), (b) OS (chemiluminescence of whole blood - CWB, levels of thiobarbituric acid reacting substance - TBARS and of HNE- and MDA-protein adducts in plasma and activity of γ-glutamyltransferase (GGT) in hind paw joint homogenates). The PI studied significantly increased the CBM of animals and corrected the HPW. STB also significantly decreased the activity of GGT in joint homogenates. SMe1 was more effective in decreasing plasmatic TBARS levels, but STB was more effective in reducing plasmatic HNE- and MDA-protein adducts. The assay for HNE- and MDA-adducts in plasma as a function of time was applied for the first time in AA. STB markedly decreased spontaneous and PMA-stimulated CWB and reduced neutrophil count. In summary, STB was more effective than SMe1 in reducing OS in AA. Our results showed that the reduction of OS in arthritis also corrected the clinical manifestations of the disease.

Combined methotrexate and coenzyme Q10 therapy in adjuvant-induced arthritis evaluated using parameters of inflammation and oxidative stress

81%

Bauerova K., Paulovicova E., Mihalova D., Drafi F., Strosova M., Mascia C., Biasi F., Rovensky J., Kucharska J., Gvozdjakova A., Ponist S.

2010

vol. 57

issue 3

347-354

Rheumatoid arthritis is a common severe joint disease that affects all age groups, it is thus of great importance to develop new strategies for its treatment. The aim of the present study was to examine the combined effect of coenzyme Q10 (CoQ10) and methotrexate (MTX) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experiments included healthy animals, arthritic animals not treated, arthritic animals treated with CoQ10, with methotrexate, and with a combination of CoQ10 and methotrexate. The two latter groups received a daily oral dose of 20 mg/kg b.w. of CoQ10, either alone or with methotrexate in an oral dose of 0.3 mg/kg b.w. twice a week. We found that CoQ10 potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect of methotrexate on the level of oxidation of proteins (suppression of protein carbonyl level in plasma) as well as lipoperoxidation (suppression of levels of HNE-adducts and MDA-adducts to plasma proteins). The same effect was observed for plasmatic levels of CoQ9 and IL-1α, and partially also for γ-glutamyltransferase activity assessed in joints and spleen. Moreover, the combination therapy improved the functionality of peripheral blood neutrophils in AA, with a balancing effect on the immunosuppression caused by MTX monotherapy. In summary, combined administration of CoQ10 and methotrexate suppressed arthritic progression in rats more effectively than did MTX alone. This finding may help improve treatment of rheumatoid arthritis.

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2 Acta Biochimica Polonica

2 2010

2 Mascia C.

2 Mihalova D.

2 Ponist S.

1 Bauerova K.

1 Bauerová K.

1 Biasi F.

1 Drafi F.

1 Gvozdjakova A.

1 Jancinova V.

1 Kucharska J.

1 Nosal R.

1 Ondrejickova O.

1 Paulovicova E.

1 Poli G.

1 Rovensky J.

1 Snirc V.

1 Stancikova M.

1 Strosova M.

Search results

Reduction of oxidative stress in adjuvant arthritis. Comparison of efficacy of two pyridoindoles: stobadine dipalmitate and SMe1.2HCl

Combined methotrexate and coenzyme Q10 therapy in adjuvant-induced arthritis evaluated using parameters of inflammation and oxidative stress