DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

Abstract

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

Terapia Fotodinâmica Em Modelo Experimental De Artrite Induzida Por Paracoccidioides Brasiliensis Terapia Fotodinâmica Em Artrite Experimental

“…Articular edema formation in the fungal-infected groups, except PDT40 and PDT120, has also been reported by other authors including Loth et al (11) and Amanai et al, (18) who used Candida albicans in an osteoarthritis model in rats. Edema caused by the pathogen was reduced and partially normal tissue aspects were observed in the joint's synovial membrane region after applying PDT to treat the arthritis caused by P. brasiliensis.…”

“…After analyzing the anti-gp43 antibody titration, the data showed greater production in the yeast group, with higher values than those presented by Loth et al (11) on day 15 of the experiment, even when using purified gp43 antigen (a glycoprotein weighing 43 kilodaltons) and using a highly specific test for this antigen. Reaction may have occurred between immunoglobulin isotypes, likely IgM.…”

“…Joint changes caused by P. brasiliensis in the experimental arthritis model showed anatomopathological aspects of fungal infection with primary involvement of the synovial membrane region in its intimal and subintimal layers, as described by Loth et al (11) .…”

“…05/2013-CE, and the experimental animal maintenance complied with the guidelines of laboratory animal use prevailing in Brazil. Male 45-day-old Wistar rats (n = 42) were used for the P. brasiliensis-induced experimental model of arthritis, (11) which mimics human articular PCM.…”

“…(8) Liang et al (8) stated that even if there was no clinical management for antifungal PDT, studies demonstrated that PDT was effective in the destruction of fungi in vitro. Wainwright et al (2017) 11 discuss the need for research with these new therapeutic agents in the fight against drug-resistant infectious diseases, being a viable alternative to conventional drugs in many fields of application. Thus, the objective of the study was to evaluate the effect of PDT on the joints of Wistar rats with arthritis induced by P. brasiliensis.…”