Antioxidant effects of gold nanoparticles on early stage of collagen-induced arthritis in rats.

OBJECTIVE: To determine antioxidant effects of prophylactic treatment with gold nanoparticles (AuNPs) in the early stage of collagen-induced arthritis (CIA). METHODS: The preventive treatment with 13 nm or 50 nm AuNPs injected intraarticularly (i.a.) was started at the induction day (0) of CIA and finished in the early stage of arthritis at the day 10. At the end of experiment blood indices (erythrocyte sedimentation rate, leukocyte and erythrocyte counts), pro-/antioxidant status of blood serum (the amount of malondialdehyde, catalase and total antioxidant activity), and internal organs' weight as well as the changes in the joint tissues and their microscopic structure were evaluated. RESULTS: Both 13 nm and 50 nm AuNPs showed antioxidant effect by increasing the level of catalase activity in the early stage of experimental arthritis. Preventive treatment with 50 nm more than with 13 nm AuNPs suppressed joint swelling. Histopathological asssesment revealed statistically significant reduction of synovial angiogenesis and erosion formation in the cartilage. Pilot transmission electron microscopy (TEM) analysis showed predominant accumulation of 13 nm in the synovial fibroblast lineage cells. CONCLUSIONS: Intraarticular injections of 13 nm or 50 nm AuNPs showed an antioxidant action significantly raising catalase activity without causing negative effects on hematological indices. Prophylactic treatment with 50 nm more than with 13 nm AuNPs suppressed joint swelling, synovial angiogenesis and cartilage erosion in the initial stage of arthritis.

The safety and efficacy of light emitting diodes-based ultraviolet A1 phototherapy in bleomycin-induced scleroderma in mice.

PURPOSE: To define the efficacy and safety of narrowband ultraviolet A1 (UVA1) for the treatment of dermal fibrosis in bleomycin-induced mouse model of scleroderma. MATERIALS AND METHODS: 42 DBA/2 strain mice were included in the study: healthy mice and mice with established scleroderma, treated with high or medium dose of UVA1. Non-treated groups served as control. The equipment emitting 365±5nm UVA1 radiation was used in the study. The average cumulative doses were 1200J/cm2 for high and 600J/cm2 for medium dose course. Histological analysis was performed for the evaluation of the dermal thickness and mast cells density. The expressions of p53 and Ki-67 proteins were assessed by immunohistochemical analyses. RESULTS: Skin thickness of mice with scleroderma, treated with high and medium dose of UVA1, were lower (272.9±113.2µm and 394±125.9µm, respectively) in comparison to the dermal thickness of non-treated animals (599±55.7µm). The dermal mast cells count in mice with scleroderma was reduced after high and medium dose treatment to 11±1.7 and 13±2.2, respectively, as compared to that in non-treated mice (23±3.0). No significant upregulation of p53 nor Ki-67 proteins was observed in the skin of healthy mice and mice with scleroderma after high- and medium-dose of UVA1. CONCLUSIONS: The results of this study indicate that 365nm UVA1 with the cumulative doses of 1200J/cm2 and 600J/cm2 is safe and effective for the dermal fibrosis treatment.

The impact of high-dose narrowband ultraviolet A1 on dermal thickness, collagen and matrix-metalloproteinases in animal model of scleroderma.

OBJECTIVE: The main purpose of the present study was to define the impact of high-dose of 365±5nm ultraviolet A1 (UVA1) on dermal fibrosis in the pre-established, bleomycin-induced mouse model of scleroderma. METHODS: DBA/2 strain mice with the pre-established, bleomycin-induced scleroderma were irradiated with cumulative UVA1 dose of 1200J/cm2 and in parallel were challenged with prolonged administration of bleomycin. Non-treated groups served as the control. Light source emitting a narrow band UVA1 light of 365±5nm and 21mW/cm2 power density was used in the study. Histological analysis was performed for the evaluation of dermal thickness. The expressions of matrix-metalloproteinase-1 (MMP-1), matrix-metalloproteinase-3 (MMP-3), collagen types I and III were evaluated by immunohistochemical analyses. The Mann - Whitney U test was used for statistical analysis. RESULTS: Dermal thickness in mice injected with bleomycin during all the experiment (8weeks) and irradiated with UVA1 for the last 5weeks was significantly lower than that in mice challenged only with bleomycin for 8weeks (253.96±31.83µm and 497.43±57.83µm, respectively; P=0.002). The dermal thickness after phototherapy was lower as compared with the pre-existing fibrotic changes observed after 3weeks of bleomycin injections (253.96±31.83µm and 443.87±41.76µm, respectively; P=0.002). High-dose of UVA1 induced the 5.8- and 5.2-fold increase in MMP-1 and MMP-3 expressions, respectively, and the 1.2- and 1.4-fold decrease in collagen type I and collagen type III expressions in the pre-established, bleomycin-induced scleroderma model as compared to that in the control non-irradiated mice (P=0.002). CONCLUSIONS: Our study has demonstrated that a cumulative 365±5nm UVA1 radiation dosage of 1200J/cm2 not only prevents the progression of dermal fibrosis, but also induces a regression of pre-existing fibrotic changes.

Anti-inflammatory and anti-oxidative effects of herbal preparation EM 1201 in adjuvant arthritic rats.

BACKGROUND AND OBJECTIVE: The purpose of the present study was to examine the anti-arthritic and antioxidant effects of herbal and active organic ingredient complex (EM 1201) in rats with experimental adjuvant arthritis (AA). MATERIALS AND METHODS: AA was induced in 30 male Wistar rats by intradermal injection of complete Freund's adjuvant into the left hind paw. The course of disease in 30 rats in response to the treatment with EM 1201 and diclofenac, the parameters including body weight, joint swelling, blood indices pro-/antioxidant status of blood serum, and histology of joints and the liver, were investigated. RESULTS: Preparation EM 1201 showed anti-inflammatory effect analogous to diclofenac, improved blood indices, significantly decreased joint swelling and histological changes in them. Joint swelling was suppressed by 29%-42.8% and 9.3%-34.4% in response to administration of EM 1201 and diclofenac during the entire experiment. Both preparations significantly suppressed pannus formation, general inflammatory reaction and edema in soft periarticular tissues and synovium, diminished MDA level and elevated AOA in the blood serum. Significantly lower absolute and relative weight of the liver and lower dystrophic processes in it, and general inflammatory infiltration of hepatic stroma proved the positive effect of treatment with EM 1201. CONCLUSIONS: The present study suggests that EM 1201 has protective activity against arthritis and demonstrated its potential beneficiary effect analogical to diclofenac. Anti-inflammatory and anti-oxidative effect of EM 1201 in rats with AA support the need of further investigations by using it as supplementary agent alone or together with other anti-arthritic drugs in the treatment of rheumatoid arthritis.

Effect of gold nanoparticles in the treatment of established collagen arthritis in rats.

BACKGROUND AND OBJECTIVE: The role of gold nanoparticles (AuNPs) in the treatment of autoimmune diseases remains vague. Therefore, the aim of this study was to determine the effect of AuNPs in the treatment of rats with established collagen-induced arthritis (CIA). MATERIAL AND METHODS: A total of 24 Wistar male rats with established CIA were used. AuNPs measuring 13-nm and 50-nm were prepared according to standard procedures, and their size was determined using transmission electron microscopy. These gold particles were injected intra-articularly 5 times a week, 12 injections in total. Body and organ weight, arthritic profiles based on paw swelling, histological changes in the joints and internal organs, blood indices, and serum oxidative products were investigated. RESULTS: An examination of the course of the experimental disease and a subsequent histological analysis as well as hematological studies revealed a nontoxic effect of AuNPs on the vital organs. The treatment of the rats with established CIA by 13-nm and 50-nm gold nanoparticles decreased joint swelling by 49.7% (P<0.002) and 45.03% (P<0.01), respectively. That corresponded to the decrease in statistically significant histological changes in articular tissues. AuNPs showed their antioxidant effect by increasing the level of antioxidant enzyme catalase. CONCLUSIONS: The continuous intra-articular administration of AuNPs not only reduced the inflammation, joint swelling, and development of polyarthritis, but also reduced histological changes in articular tissues without toxic effects on the internal organs. The results obtained disclose the role of AuNPs as antioxidant agents.

Anti-inflammatory activity of some potassium salts of N,N-disubstituted 4-aminoazobenzenesulfonic acids in rat adjuvant arthritis.

Anti-inflammatory effects of three potassium salts of N,N-disubstituted 4-aminoazobenzenesulfonic acids were investigated and compared to that of acetylsalicylic acid (ASA) in rats with adjuvant arthritis (AA). Prophylactic oral administration of all compounds in a dose of 150 mg/kg ameliorated AA symptoms in animals. The most pronounced anti-inflammatory activity at the end of the experiment showed compound 1 containing imino group: it significantly suppressed joint swelling by 48.2% in female and by 44.2% in male rats with AA. The development of polyarthritis after the treatment with this compound was the lowest in female (20%) and male (40%) rats (in control--100% of animals with polyarthritis). All derivatives, and especially compound 1, also improved the systemic parameters of disease such as blood indices and internal organs' weight, and showed no toxicity on the main organs such as liver and spleen.

Spectroscopic study of ALA-induced endogenous porphyrins in arthritic knee tissues: targeting rheumatoid arthritis PDT.

The inflamed synovium of rheumatoid arthritis exhibits many features typical for neoplastic tissue implying that the photodynamic therapy might be an efficient modality for chronic poliarthritis. The accumulation of endogenously produced porphyrins after administration of exogenous 5-aminolevulinic acid (ALA) in a rabbit model of rheumatoid arthritis was evaluated by fluorescence spectroscopy. Independent of the way, intravenously or intra-articularly, in which ALA was administered to the experimental animals, the highest fluorescence intensity of endogenously produced porphyrins was detected in the tissues of the inflamed joints. Besides, the application of ALA had a systemic sensitising effect on the whole organism of rabbits. The highest amount of endogenously produced porphyrins in the inflamed joints measured from the surface of the skin above the synovium tissues was detected 1-3 h after the administration of ALA. Fluorescence measurements performed on the tissue specimens ex vivo showed the predominant accumulation of porphyrins in the synovium of the inflamed joints. The fluorescence of porphyrins was also observed in the cartilage tissues taken from knee joints. However, the fluorescence spectra features indicated that the composition of porphyrins detected in the cartilage tissues was different than that in the synovial tissues. The selective accumulation of porphyrins in the inflamed synovial tissues stands up for the application of photodynamic therapy in the treatment of rheumatoid arthritis and implies the possibility to use optical non-invasive methods based on fluorescence detection of endogenously produced porphyrins for diagnostics of inflamed tissues.

[Proinflammatory cytokine interleukin-17 and its role in pathogenesis of rheumatoid arthritis]. / Uzdegima skatinancio citokino interleukino-17 vaidmuo reumatoidinio artrito patogenezeje.

This is a review concerning the role of interleukin-17, a proinflammatory cytokine, produced by activated memory CD4+ T cells, in pathogenesis of rheumatoid arthritis. As interleukin-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. Interleukin-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.