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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]

Transcutol® is a perfect solubilizer and an effective permeation enhancer of many active substances commonly used in cosmetics. Microemulsions due to the content of surfactant and co-surfactant could be also considered as chemical permeation enhancers that may support transdermal delivery of poorly water- soluble drugs. The purpose of this study was to investigate the effect of Transcutol® and potential microemulsions on diffusion of poorly soluble indomethacin through an artificial membrane and excised rat skin. After drug solubilization in different enhancers, drug was dispersed in sodium alginate or carbopol gel used as dermal basis. For characterization of the microemulsions, the basic physico-chemical properties were determined. In vitro as well as ex vivo drug release was determined by vertical Franz cells. Enhancing effect of the examined microemulsions was observed only in carbopol gel. There was an increase in cumulative drug amount released through synthetic membrane by 37.7–39.8% from the microemulsion formulation and 90.6% from Transcutol® formulation within 6 h compared to the control samples. The differences between the permeation curves with or without the content of the enhancers were statistically significant (p <.05). Pearson correlation coefficients indicate a very high degree of dependence (r > 0.9) between in vitro and ex vivo drug release from all dermal vehicles used. It can be stated that Transcutol® is the best solubilizer and also penetration enhancer from the examined, and therefore it seems to be effective excipient/solubilizer in topical IND formulation. [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]

The antioxidant capacities of curcumin and turmeric extract were determined and compared. Turmeric extract showed higher values of antioxidant power normalized to curcumin content (31.9%) in a majority of antioxidant assays than the curcumin standard. The particular half-maximal inhibitory concentration (IC50) values for curcumin were 2.34 µg⋅ml-1 in the 1,1′-diphenyl-2-picrylhydrazyl (DPPH) test, and 0.21 mg⋅ml-1 in the liposomal peroxidation assay in the extract, compared to IC50 = 3.33 µg⋅ml-1 and 0.343 mg⋅ml-1 in the curcumin standard, respectively. Conversely, a significantly lower IC50 of curcumin (0.020 mg⋅ml-1) for 12-lipoxygenase (LOX) inhibition was obtained than that of C. longa extract (2.95 mg⋅ml-1). The reactivity of the samples tested in the particular assays correlated well with the redox potentials of the model oxidants. In the liposomal system, the antioxidant activity may be influenced by the distribution processes at the phase interface. In conclusion, our results suggest that curcumin and its analogues may be decisive for the free radical-scavenging capacity of the turmeric extract. [ABSTRACT FROM AUTHOR]

Objectives: To assess glucomannan and pyridoindole derivatives for possible antioxidant therapy of rheumatoid arthritis (RA) by using the model of adjuvant arthritis (AA). We evaluated the association between clinical markers of the adjuvant arthritis model used - increase of hind paw volume (HPV), changes of body mass (CBM), and tissue gamma-glutamyl transferase (GGT) activity assessed in the spleen and the joint., Methods: AA was induced in Lewis rats by a single intradermal injection of Mycobacterium butyricum. The two independent experiments included healthy animals as reference, arthritic animals without any drug administration and arthritic animals with pyridoindole administration in one dose tested or glucomannan administration in two different doses. The pyridoindoles (PI) studied were stobadine dipalmitate and its derivatives SMe1.2HCl and SMe1EC2.HCl. We monitored CBM and HPV twice a week. Parameter of inflammation - GGT in the spleen and the joint from the hind paw (cartilage and soft tissue without bone) was determined on day 28. The correlation coefficient of GGT activity with CBM and with HPV was calculated., Results: The antioxidants tested were effective in slowing down the progress of adjuvant arhritis. The association between tissue GGT activity and the clinical marker of adjuvant arthritis - CBM was higher in the spleen than in the joint. The other clinical marker assessed - HPV, gave a better association with GGT activity measured in the joint than in the spleen., Conclusions: It may be concluded that GGT activity in tissues as the spleen and the joint could provide a simple and inexpensive marker for AA and RA development at systemic as well as local level; all the antioxidants studied were effective in slowing down the progress of adjuvant arhritis.