Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis.

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by inflammation that affects not only the liver but also other organs and the musculoskeletal system. The standard therapy for RA is methotrexate (MTX), which has safety limitations. The extract from Crocus sativus L. (saffron-SF) is also known for its anti-inflammatory effects. Therefore, we decided to investigate the potential benefit of SF in monotherapy via two doses (SF1-25 mg/kg of b.w.; SF2-50 mg/kg of b.w.) and in combination with MTX (0.3 mg/kg of b.w., twice a week) using adjuvant arthritis in rats. To evaluate these therapeutic settings, we used biometric, immunological, and biochemical parameters, as well as the relative gene expression of the mRNA in the liver. Our results showed a statistically significant increase in the experimental animals' body weight and the arthritic score (AS) on day 14 for monotherapy with SF1 and SF2. The change of hind paw volume (CHPV) was significant only for SF2 monotherapy on the 14th day of the experiment. A combination of SF1 and SF2 with MTX significantly modulated all the biometric parameters during the experimental period. Additionally, AS and CHPV improved considerably compared to MTX monotherapy on day 21. Furthermore, all monotherapies and combination therapies were significant for the biochemical parameter γ-glutamyl transferase (GGT) in the joint. GGT activity in the spleen was less pronounced; only MTX in combination with SF1 significantly modified this parameter. The higher dose of SF monotherapy (SF2) was similarly significant with respect to immunological parameters, such as plasmatic IL-17A, IL-1ß, and MMP-9 on day 21. The combination of both doses of SF with MTX significantly improved these immunological parameters, except for C-reactive protein (CRP), which was influenced only by the higher dose of SF2 in combination with MTX in plasma at the end of the experiment. A different effect was found for the relative expression of CD36 mRNA, where only SF1 significantly decreased gene expression in the liver. However, the relative gene mRNA expression of IL-1ß in the liver was significantly reduced by the SF monotherapies and the combination of both SF doses with MTX. Our findings showed SF's partial antiarthritic and anti-inflammatory potential in monotherapy, but the effect was stronger in combination with MTX.

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis.

Rhodiola rosea L. extract (RSE) is mostly known for its adaptogen properties, but not for its antiarthritic activities, therefore monotherapy and combination with low-dose methotrexate (MTX) was studied. The collagen-induced arthritis (CIA) model was used to measure the functional score, and the change in hind paw volume (HPV). Both parameters had significant antiarthritic effects. Based on these preliminary results, an adjuvant arthritis (AA) model was further applied to assess another parameters. The experiment included these animal groups: healthy controls, untreated AA, AA administered with RSE (150 mg/kg b.w. daily, p.o.), AA administered by MTX (0.3 mg/kg b.w. twice a week, p.o.), and AA treated with the combination of RSE+MTX. The combination of RSE+MTX significantly reduced the HPV and increased the body weight. The combination significantly decreased HPV when compared to MTX monotherapy. The plasmatic levels of inflammatory markers (IL-6, IL-17A, MMP-9 and CRP) were significantly decreased by MTX+RSE treatment. The RSE monotherapy didn't influence any of the inflammatory parameters studied. In CIA, the RSE monotherapy significantly decreased the arthritic parameters studied. In summary, the combination of RSE and sub-therapeutic MTX was significantly effective in AA by improving inflammatory and arthritic parameters.

Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?

Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer's disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading to dementia and death, is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aß) and the intraneuronal deposits of neurofibrillary tangles (NFTs) consisting of altered hyperphosphorylated tau protein. Both have been widely studied and pharmacologically targeted for many years, without significant therapeutic results. In 2022, positive data on two monoclonal antibodies targeting Aß, donanemab and lecanemab, followed by the 2023 FDA accelerated approval of lecanemab and the publication of the final results of the phase III Clarity AD study, have strengthened the hypothesis of a causal role of Aß in the pathogenesis of AD. However, the magnitude of the clinical effect elicited by the two drugs is limited, suggesting that additional pathological mechanisms may contribute to the disease. Cumulative studies have shown inflammation as one of the main contributors to the pathogenesis of AD, leading to the recognition of a specific role of neuroinflammation synergic with the Aß and NFTs cascades. The present review provides an overview of the investigational drugs targeting neuroinflammation that are currently in clinical trials. Moreover, their mechanisms of action, their positioning in the pathological cascade of events that occur in the brain throughout AD disease and their potential benefit/limitation in the therapeutic strategy in AD are discussed and highlighted as well. In addition, the latest patent requests for inflammation-targeting therapeutics to be developed in AD will also be discussed.

Enhanced Anti-Inflammatory Effect of the Combination of Lactiplantibacillus plantarum LS/07 with Methotrexate Compared to Their Monotherapies Studied in Experimental Arthritis.

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.

Implementation and Access to Pre-exposure Prophylaxis for Human Immunodeficiency Virus by Men Who Have Sex With Men in Europe.

Pre-exposure prophylaxis (PrEP) is a significant public health intervention with proven efficacy and safety in the prevention of human immunodeficiency virus (HIV) infection, which has taken a considerable amount of time to reach Europe in relation to their transatlantic counterparts, namely, the United States of America (USA). There, it is perceived as being an essential prevention tool to be integrated within existing medical, behavioral and structural interventions in place for the management and containment of HIV infection in men who have sex with men (MSM). In a region such as Europe, with approximately double the USA population, it is estimated that not even 10% have proper access to PrEP, and given the lack of coordination with healthcare, taking PrEP has to be at their own expense. Here, we identify the reasons behind the 4-year lag in the approval of PrEP in the European Union/European Economic Area (and Europe in general) and explore the efficacy and effectiveness of PrEP needed to be confirmed with some implementation or demonstration studies conducted in the region. Independent of the data gathered, access of MSM to PrEP is far from ideal in Europe and much still needs to be done. The demonstration of the cost-effectiveness of PrEP alongside other social and behavioral factors needs to be addressed, while the clear populations within MSM that will benefit from this intervention are properly identified and make use of the latest recommendations of the World Health Organization that consider not only daily PrEP but also event-driven PrEP. The momentum for the proper implementation of PrEP in the EU is not lost, and with the existence of generics and even new formulations, there is a renewed opportunity for unleashing the public health benefits arising from this pharmacological tool with other interventions in place (e.g., condoms, testing, and counseling).

Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis.

Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)-an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO-control, AIA-untreated adjuvant-induced arthritis, AIA-BIL-adjuvant-induced arthritis administrated UCB, CO-BIL-control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund's adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.

Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis.

Anti-inflammatory potential of orally administrated bioflavonoid-robinin, active sub-stance of original drug Flaroninum™ (FL), was investigated in the combination with methotrexate (MTX) and in monotherapy in rats suffering from adjuvant-induced arthritis (AA). Robinin (kaempferol-3-O-robinoside-7-O-rhamnoside) was isolated from the aerial parts of Astragalus falcatus Lam. The monotherapy with robinin was not efficient in alleviating symptoms of AA. The combination of MTX with robinin was similarly active as MTX alone in reducing the hind paw volume and change of body weight during the whole experiment. The combination, however, reduced plasma levels of Interleukin-17Aand activity of gamma-glutamyl transferase in joint more efficiently then MTX alone. Our results demonstrate that the novel combination of robinin and MTX mildly improved the reduction of inflammation in experimental arthritis.

Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells.

Ovarian cancer is one of the most common malignancies in women and contributes greatly to cancer-related deaths. Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor gene located at chromosomal region 8p22, which is often lost in epithelial cancers. Epigenetic silencing of TUSC3 has been associated with poor prognosis, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. However, the precise molecular role of TUSC3 in ovarian cancer remains unclear. In this study, we establish TUSC3 as a novel ovarian cancer tumor suppressor using a xenograft mouse model and demonstrate that loss of TUSC3 alters the molecular response to endoplasmic reticulum stress and induces hallmarks of the epithelial-to-mesenchymal transition in ovarian cancer cells. In summary, we have confirmed the tumor-suppressive function of TUSC3 and identified the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.

Markers of inflammation and oxidative stress studied in adjuvant-induced arthritis in the rat on systemic and local level affected by pinosylvin and methotrexate and their combination.

Oxidative stress (OS) is important in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and its experimental model--adjuvant arthritis (AA). Antioxidants are scarcely studied in autoimmunity, and future analyses are needed to assess its effects in ameliorating these diseases. Although there are studies about antioxidants effects on the course of RA, their role in combination therapy has not yet been studied in detail, especially on extra-articular manifestations of AA. During the 28-d administration of pinosylvin (PIN) in monotherapy and in combination with methotrexate (MTX) to AA rats, we evaluated the impact of the treatment on selected parameters. The experiment included: healthy controls, untreated AA, AA administered 50 mg/kg b.w. of PIN daily p.o., AA administered 0.4 mg/kg b.w. of MTX twice weekly p.o. and AA treated with a combination of PIN+MTX. AA was monitored using: hind paw volume, C-reactive protein, monocyte chemotactic protein-1 (MCP-1), thiobarbituric acid reactive substances (TBARS) and F2-isoprostanes in plasma, γ-glutamyltransferase activity in spleen, activity of lipoxygenase (LOX) in lung, heme oxygenase-1 (HO-1) and nuclear factor kappa B (NF-κB) in liver and lung. PIN monotherapy significantly improved the activation of NF-κB in liver and lung, HO-1 expression and activity of LOX in the lung, MCP-1 levels in plasma (on 14th d) and plasmatic levels of F2-isoprostanes. An important contribution of PIN to MTX effect was the reduction of OS (an increase of HO-1 expression in lung and reduction of plasmatic TBARS) and decrease of LOX activity in the lung.

Effect of nonanimal high- and low-molecular-mass chondroitin sulfates produced by a biotechnological process in an animal model of polyarthritis.

BACKGROUND/AIMS: We planned to report on the effect of two nonanimal chondroitin sulfates (CSs) with different molecular masses produced using an innovative biotechnological process in an adjuvant arthritis animal model. METHODS: The experiments included healthy animals, untreated arthritic animals and arthritic animals having been administered 900 mg/kg of either of the two CS samples daily. Arthritic score, γ-glutamyltransferase (GGT) activity in hind paw joint tissue homogenates, plasmatic C-reactive protein (CRP) and pro-inflammatory cytokines IL-1ß and IL-6 were assayed. RESULTS AND CONCLUSIONS: Low-molecular-mass (LMM) CS significantly reduced the arthritic score by up to about 30% from 14 to 28 days. In contrast, no significant differences were observed for high-molecular-mass (HMM) CS, even if a trend in its capacity to decrease the arthritic score by up to about 11% was observed. Additionally, LMM CS was able to significantly decrease GGT activity by approximately 31% and plasmatic CRP levels by about 9%. Both nonanimal CS samples were effective in reducing plasmatic levels of proinflammatory cytokines. A greater efficacy was also observed for LMM CS compared with a pharmaceutical-grade CS of extractive origin, while the efficacy of the HMM CS sample was found to be rather similar. The greater effect of LMM CS in reducing arthritic parameters may be related to its lower molecular mass with respect to HMM CS and natural CS.

N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis.

Many of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N-f-5HT in the oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N-f-5HT and MTX. N-f-5HT in monotherapy reduced only activation of NF-κB and did not have any significant effect on other parameters monitored. Low-dose treatment of MTX decreased the level of IL-1ß and MCP-1 on day 14 and activation of NF-κB in liver without significant effect on other parameters. N-f-5HT and MTX combination showed both the anti-arthritic (hind paw volume and arthritic score) and anti-inflammatory effect (plasmatic levels of IL-1ß, IL-17, MCP-1, CRP, and activation of NF-κB in liver). In combination with MTX, N-f-5HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA.

Blind deconvolution in dynamic contrast-enhanced MRI and ultrasound.

This paper is focused on quantitative perfusion analysis using MRI and ultrasound. In both MRI and ultrasound, most approaches allow estimation of rate constants (Ktrans, kep for MRI) and indices (AUC, TTP) that are only related to the physiological perfusion parameters of a tissue (e.g. blood flow, vessel permeability) but do not allow their absolute quantification. Recent methods for quantification of these physiological perfusion parameters are shortly reviewed. The main problem of these methods is estimation of the arterial input function (AIF). This paper summarizes and extends the current blind-deconvolution approaches to AIF estimation. The feasibility of these methods is shown on a small preclinical study using both MRI and ultrasound.

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 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.

Aurothiomalate as preventive and chain-breaking antioxidant in radical degradation of high-molar-mass hyaluronan.

The potential anti- or pro-oxidative effects of a disease-modifying antirheumatic drug, aurothiomalate, to protect high-molar-mass hyaluronan against radical degradation were investigated along with L-glutathione - tested in similar functions. Hyaluronan degradation was induced by the oxidative system Cu(II) plus ascorbate known as the Weissberger's oxidative system. The time- and dose-dependent changes of the dynamic viscosity of the hyaluronan solutions were studied by the method of rotational viscometry. Additionally, the antioxidative activity of aurothiomalate expressed as a radical-scavenging capacity based on a decolorization 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay was inspected. At the higher concentrations tested, L-glutathione showed excellent scavenging of (.) OH and peroxyl-type radicals, however, at the lowest concentration applied, its pro-oxidative effect was revealed. The effects of aurothiomalate on hyaluronan degradation were similar to that of L-glutathione, however, at the lowest concentration tested, no significant pro-oxidant effect was observed.

Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress.

As a number of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration, increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The safety of long-term therapy of RA is very important as patients with RA are usually treated for two or more decades. This experimental overview is focused on some promising substances and their combinations with the standard antirheumatic drug - methotrexate (Mtx) for treatment of rheumatoid arthritis. The adjuvant arthritis model in Lewis rats was used for evaluation of antiinflammatory efficacy of the substances evaluated. Mtx was administered in the oral dose of 0.3 mg/kg b.w. twice a week. Natural and synthetic antioxidants were administered in the daily oral dose of 20 mg/kg b.w for coenzyme Q(10) (CoQ(10)), 150 mg/kg b.w for carnosine (Carn), 15 mg/kg b.w. for stobadine dipalmitate (Stb) and its derivative SMe1.2HCl (SMe1), and 30 mg/kg b.w. for pinosylvin (Pin) or pterostilbene (Pte). Mtx in the oral dose of 0.4 mg/kg b.w. twice a week was combined with Pin in the oral daily dose of 50 mg/kg b.w. Clinical (hind paw volume - HPV), biochemical (activity of GGT in joint and level of TBARS in plasma), and immunological (IL-1 in plasma) parameters were assessed. Our results achieved with different antioxidants in monotherapies showed a reduction of oxidative stress in adjuvant arthritis independently of the chemical structure of the compounds. Pin was the most effective antioxidant tested in decreasing HPV. All combinations tested showed a higher efficacy in affecting biochemical or immunological parameters than Mtx administered in monotherapy. The findings showed the benefit of antioxidant compounds for their use in combination therapy with methotrexate.

Carnosine inhibits degradation of hyaluronan induced by free radical processes in vitro and improves the redox imbalance in adjuvant arthritis in vivo.

OBJECTIVE: New ways of supplementary or combinatory therapy of rheumatoid arthritis (RA) are of great importance. The aim is to find an additive to classical RA therapy with natural molecules without side effects possessing anti-inflammatory and anti-oxidative properties. In this study we investigated the anti-oxidative and anti-inflammatory properties of the endogenous natural compound carnosine (CARN) in vitro and in vivo. Moreover, we tested also the inhibitory properties of the drug methotrexate (MTX) on dynamic viscosity of hyaluronan (HA) solutions in the same manner. METHODS: For in vitro testing of the inhibitory properties of CARN against degradation of HA solutions, we used the model of degradation of hyaluronan (HA) induced by free radicals. Both substances, CARN and MTX, were compared to glutathione (GSH). Rotational viscometry was used in evaluation of protective properties of compounds studied. The ability of CARN to restore the redox imbalance occurring in adjuvant arthritis (AA) of rats was also tested. We monitored the effect of CARN on hind paw volume (HPV) and on the levels of protein carbonyls, and thiobarbituric acid reacting substances (TBARS) in AA. RESULTS: In the reaction system with the prevalence of •OH and/or peroxy-type radicals, CARN in 200 µmol/L concentration tested was shown to exert a protective action on HA degradation. MTX was less effective than CARN in preventing HA degradation. Its ability to protect HA against radical degradation was evident only at the highest concentration of 400 µmol/L. In AA, carnosine significantly reduced TBARS and protein carbonyls in plasma, and also decreased the HPV of animals most effectively on the day 14. CONCLUSIONS: CARN proved its inhibitory properties against degradation of HA solutions at experimental conditions in vitro and showed its beneficial efficiency in vivo. Moreover, it reduced also HPV, the clinical marker of inflammation in AA.

Ascorbate and Cu(II)-induced oxidative degradation of high-molar-mass hyaluronan. Pro- and antioxidative effects of some thiols.

OBJECTIVE: This study presents the results of antioxidative and pro-oxidative efficacy of cysteamine and D-penicillamine (D-pen) in comparison to L-glutathione (L-GSH) on high-molar-mass hyaluronan (HA) degradation by cupric ions plus ascorbic acid. METHODS: The substance tested was applied in the degradative system cupric ions plus ascorbate: (i) before the reaction onset or also (ii) 1 h after the reaction started. The results obtained were compared with that one recorded by using the degradative system in the absence of the substance tested. To monitor HA degradation kinetics, rotational viscometry was applied. Moreover, the standard ABTS and DPPH assays were used. RESULTS: By using the method of rotational viscometry, D-pen showed dual effect: initial inhibitory effect on •OH radicals was changed to a pro-oxidative one in the dose and time dependent manner. Both L-GSH and cysteamine were recorded to be more effective scavengers of •OH radicals than D-pen. Cysteamine demonstrated to be an excellent scavenger also of alkoxyl- and peroxyl- type radicals. Based on IC50 values, gained by ABTS assay, it is evident that D-pen showed higher radical scavenging capacity compared to cysteamine. Similar results were observed also in DPPH assay, although in this assay less effective radical scavenging capacities of both substances tested were recorded. CONCLUSIONS: On the basis of the results obtained, it can be stated that D-pen can produce hydrogen peroxide or •OH radicals and can inhibit the production of these oxidants. Our results showed that both L-GSH and cysteamine are similarly effective in inhibiting of HA degradation. Moreover, cysteamine demonstrated to be a significant inhibitor of alkoxyl- and peroxyl- type radicals generated from C-type macroradical of HA.

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

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.