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This in vivo study performed in rat adjuvant arthritis aims to advance the understanding of astaxanthin's therapeutic properties for the possible treatment of rheumatoid arthritis (RA) in monotherapy and along with the standard RA treatment, methotrexate (MTX), in combination therapy. The main goal was to elucidate astaxanthin's full therapeutic potential, evaluate its dose dependency, and compare its effects in monotherapy with other carotenoids such as β-carotene and β-cryptoxanthin (KXAN). Moreover, potential differences in therapeutic activity caused by using different sources of astaxanthin, synthetic (ASYN) versus isolated from Blakeslea trispora (ASTAP), were evaluated using one-way ANOVA (Tukey-Kramer post hoc test). KXAN was the most effective in reducing plasma MMP-9 levels in monotherapy, significantly better than MTX, and in reducing hind paw swelling. The differences in the action of ASTAP and ASYN have been observed across various biometric, anti-inflammatory, and antioxidative parameters. In combined therapy with MTX, the ASYN + MTX combination proved to be better. These findings, especially the significant anti-arthritic effect of KXAN and ASYN + MTX, could be the basis for further preclinical studies. [ABSTRACT FROM AUTHOR]

The gut microbiome (GM) of rheumatic arthritis (RA) patients is often altered in composition and function. Moreover, methotrexate (MTX), one of the most frequently used disease-modifying antirheumatic drugs, is known to negatively affect GM composition. The modulation of immune system activity is one of the therapeutic benefits of probiotics. The aim of the current investigation was to determine the impact of MTX therapy combined with one of the Lactobacillus strains, Lactoplantibacillus plantarum LS/07 (LB), on adjuvant arthritis (AA) in rats. Methods focused on biometric and inflammatory parameters in AA, particularly on plasmatic levels of IL-17A, MMP-9, and MCP-1, and the activities of gamma-glutamyl transferase in the spleen and joints were applied. Enhancing the effect of MTX, LB positively influenced all biometric and inflammatory parameters. The findings of the present study may be of help in proposing novel therapeutic strategies for RA patients. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) and its animal model adjuvant arthritis (AA) are inflammatory diseases characterized by chronic inflammation, systemic oxidative stress and disturbed mitochondrial bioenergetics of skeletal muscle. The present study aimed to evaluate the effects of coenzyme Q10 - CoQ10 (100 mg/kg b.w.), omega-3-polyunsaturated fatty acids - 1-3-PUFA (400 mg/kg b.w.) and their combined treatment in AA on impaired skeletal muscle mitochondrial bioenergetics, inflammation and changes in levels CoQ9 and CoQ10 in plasma. Markers of inflammation (C-reactive protein, monocytechemotactic protein-1), antioxidant capacity of plasma, respiratory chain parameters of skeletal muscle mitochondria and concentrations of CoQ9 and CoQ10 in plasma and in muscle tissue were estimated. Treatment of the arthritic rats with CoQ10, 1-3-PUFA alone and in combination partially reduced markers of inflammation and increased antioxidant capacity of plasma, significantly increased concentrations of coenzyme Q in mitochondria and improved mitochondrial function in the skeletal muscle. Combined treatment has similar effect on the mitochondrial function as monotherapies; however, it has affected inflammation and antioxidant status more intensively than monotherapies. Long-term supplementary administration of coenzyme Q10 and 1-3-PUFA and especially their combination is able to restore the impaired mitochondrial bioenergetics and antioxidant status in AA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX. [ABSTRACT FROM AUTHOR]

During rheumatoid arthritis (RA), there is a shift in redox balance. Natural compounds play a major role as an adjuvant in reducing the symptoms of RA. In this study we evaluated the effect of carotenoids (astaxanthin, beta-carotene, and beta-cryptoxanthin) in monotherapy or in combination therapy with methotrexate (MTX) on clinical parameters during adjuvant arthritis (AA). Male Lewis rats were divided into 8 groups. The AA was induced by an injection of Mycobacterium butyricum into the base of the tail. The clinical data were assessed every 7 days until the 28th day. MTX was administrated twice a week (0.3 mg/kg of body weight). Synthetic astaxanthin (ASYN, 20 mg/kg) and natural astaxanthin (ASTAP, 20 mg/kg, source: Blakeslea trispora) were both administrated alone and in combination with MTX. Dosage of beta-carotene was 20 mg/kg and of beta-cryptoxanthin was 10 µg/kg. Administration per os was used. In amelioration of the weight loss caused by arthritis we observed that combination of both astaxanthins with MTX was more effective as MTX alone. Further all carotenoids improved this parameter also in monotherapy. ASTAP had the highest effect. In the most important clinical outcome--changes of the hind paw volume--were all carotenoids effective excluding beta-carotene and ASYN. In conclusion, carotenoids could be a prospective addition to RA therapy. Further evaluation of inflammation and oxidative stress should be aimed. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated anti-inflammatory and chondroprotective properties of hyaluronic acid (HA) in rheumatoid arthritis. This study aimed to examine the combination of HA and methotrexate (MTX) in rats suffering from adjuvant arthritis (AA). In our studies, we used male Lewis rats and the arthritis was induced with Mycobacterium butyricum. The experiments included healthy controls, arthritic animals not treated, arthritic animals treated with HA or MTX, and arthritic animals treated with the combination of HA and MTX. Animals received daily doses of 0.5 mg and 5 mg/kg b.w. of HA of varying molecular weights (0.43, 0.99, and 1.73 MDa) alone or combined with MTX in an oral dose of 0.3 mg/kg b.w. twice weekly. We measured improving effect of HA on antioxidant enzymes in erythrocytes (superoxide dismutase and glutathione peroxidase) and on plasma antioxidant capacity. Moreover, we found that HA reduced a marker of oxidative damage of lipids in plasma--the level of lipid hydroperoxides. Most significant was the effect of HA with higher molecular weight. Finally, combined administration of HA and MTX suppressed arthritic progression in rats more effectively than MTX alone. There is a possibility that this finding will lead to improved treatments for rheumatoid arthritis patients. [ABSTRACT FROM AUTHOR]

In this study we investigated the potential antioxidant effect of carnosic acid and its combination with methotrexate (MTX) on mRNA expression of catalase (CAT) and heme oxygenase 1 (HO-1) in the liver as key parameters of oxidative stress in rat adjuvant arthritis (AA). We also examined arthritic score (AS) as representative clinical parameter monitored in this animal model. MTX was administrated in a subtherapeutic dose twice a week of 0.3 mg/kg b.w. The carnosic acid (CA) was administered daily in a dose of 100 mg/kg b.w., alone and in combination with MTX (CA+MTX). CA and MTX were administrated orally by gastric gavage. Plasma samples were collected on the 28th experimental day and used for PCR determination. The 28th experimental day was also used for AS analysis. We observed a significant decrease of CAT expression in the liver in the nontreated AA animal group, which indicated successful induction of AA. In MTX and CA groups, we did not observe any significant increment of CAT, but in the group with combination therapy, there was a significant increase of CAT expression compared to the AA group and to the MTX group itself. Expression of HO-1 was significantly increased in the AA group compared to the control group. MTX and CA groups did not significantly improve the levels of HO-1, but in CA+MTX we observed a significant decrease compared to the AA group. In the clinical parameter AS, we observed a very similar result as with markers of oxidative stress, meaning that CA+MTX was the only group that significantly lowered AS compared to the AA group. Monotherapy with CA as well as with MTX had no significant effect in our experiment on all evaluated parameters. Combination of CA and MTX has been proven to be more efficient than MTX in monotherapy, which might have promising effects in reducing side effects of MTX treatment by lowering the dose of MTX. [ABSTRACT FROM AUTHOR]