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.
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.
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.
The aim of this study was to investigate the development of collagen-induced arthritis (CIA) in male and female Wistar and Lewis rats and establish relationships between clinical status and the levels of serum oxidative products. CIA was induced in 64 rats divided randomly into three groups. Animals of the 1st group received one 0.1 ml injection of bovine type II collagen (CII, in dose of 0.1 mg/rat) emulsified in incomplete Freund's adjuvant (IFA). Rats of the 2nd group were immunized twice: on day 0 (dose of CII 0.1 mg/rat) and day 7 (dose of CII 0.05 mg/rat), and the animals of the 3rd group received one 0.1 ml injection of emulsion consisting of CII (0.1 mg/rat) in IFA and muramyldipeptide (MDP, in dose of 3 mg/ml). Serum oxidative products such as malondialdehyde (MDA), anti-oxidative enzyme catalase (CAT), total antioxidant activity (AOA), and arthritic profiles based on paw swelling, development of polyarthritis and histological changes in joints were measured in rats with CIA. Our findings have demonstrated that CIA develops in both sexes of Wistar and Lewis rats and the disease that occurs is an inflammatory erosive arthritis. Examination of the clinical course of the disease and the subsequent histological analysis disclosed a slight less aggressive disease in Wistar than in Lewis rats and in female than in male animals. The most severe arthritis developed in the 3rd group of male Lewis rats. CIA induced significant changes in the parameters of the pro-/antioxidant status of serum. Comparison of the oxidative statuses of both strains of rats with CIA and those of healthy animals revealed more elevated MDA levels in the serum of Wistar than Lewis rats. More evidently in the serum of these rats the level of total AOA was reduced, especially in the 3rd group of animals. More susceptible to CIA, Lewis rats showed a lower MDA production as compared with Wistar animals, and the lowest CAT activity in the serum of these rats was observed. In conclusion, attenuated inflammatory response and pathomorphological changes in joints were more observed in female animals of both strains. Male Lewis rats were most susceptible to CIA. On the basis of increased lipid peroxidation and decreased levels of AOA and enzyme CAT activity, CIA rats are subject to oxidative stress.
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