O efeito do óleo de copaíba (Copaifera spp.) sobre a morfologia das articulações de camundongos na artrite aguda induzida por Zymosan

Abstract

Rheumatoid arthritis (RA) is a disease that mainly affects the joints, with key pathogenic alterations being attributed to the synovial membrane (SM). Available treatments for the disease are effective in minimizing symptoms, but their ability to intervene in disease progression and joint destruction is still limited, in addition to having numerous adverse effects. In this sense, the administration of natural products has emerged as an option. In this scenario, copaiba oil has been the subject of several studies aiming to prove them or adapt them to new therapies. Although widely studied, its action on key events in RA, such as hyperplasia and synoviocyte activation, immune cell infiltration and tissue invasion, need to be elucidated. Objective: To investigate the effect of copaiba oil (Copaifera spp.) on structural and ultrastructural morphology of joints in mice in acute arthritis induced by Zymosan (Zy), especially on the synovial membrane. Materials and methods: Balb/c mice were induced to AZy by s.c. injection of 500µg Zy solution into the paw. Two groups were destined to the evaluation of the oil, being administered, through the orogastric route (o.g.), 300 and 600 mg/kg. For comparison, groups treated with conventional treatment (diclofenac), without pharmacological intervention (Control) and treated only with oil (Control Copaíba) were used. 96 hours after the injection, the paws and tissues were removed for histomorphological, stereological and electron microscopy analysis. Results: The injection of Zy in the paw was effective and developed edema and morphological and morphometric changes in small joints (metatarsal and phalanx), from which UL hyperplasia stands out, which resulted in an increase in its volume and surface space, bone erosion and cartilage loss, which in turn, presented reduced volume and surface. Copaiba oil proved to be effective in preserving the morphology and morphometry of the joint and its components, showing great similarity to conventional control and treatment. However, in relation to edema, it proved to be effective only in the first hours (1h and 3h), losing its capacity during the experiment. Arthritic SD showed classic ultrastructural changes, such as hyperplasia with inflammatory infiltrate, rich synoviocytes B with increased rER and cytoplasmic vacuoles, dilated cisterns filled with ribosomes and extensive cytoplasmic processes, and synoviocytes A with numerous cytoplasmic vacuoles. Copaiba oil conferred plasticity on the synoviocytes, which arranged themselves in such a way as to make the membrane impermeable. Conclusion: The AZy model is effective in developing structural and ultrastructural changes in small joints when applied to the paw via sc Copaiba oil has shown promise in containing morphological and morphometric changes imposed by experimental arthritis by Zy, which were evidenced by stereology and electron microscopy. However, additional studies are needed to elucidate the mechanisms involved and adjust the dose and period of administration of the natural product.

Keywords: Zymosan, stereology, morphology, electron microscopy, animal model.