Cyclosporin a Reduces Airway Mucus Secretion and Mucociliary Clearance in Rats

Abstract

-Filho G, Jatene FB. Cyclosporine A reduces airway mucus secretion and mucociliary clearance in rats. Clinics. 2007:62(3):345-52. PURPOSE:To assay the effects of cyclosporin A on mucus secretion from goblet cells and on mucociliary transport in situ in rats. METHODS: Twenty-one male Wistar rats were assigned to 3 groups: control (n = 5), saline (n = 8), and cyclosporin A (n = 8). After 30 days of drug therapy, the rats were killed, and the lungs were removed from the thoracic cavity. Mucus samples were collected, and the transport rate was evaluated in vitro using a bullfrog palate model. Mucociliary transport was timed in situ by direct view of particles trapped on the mucus moving across the respiratory tract. Finally, the amount of stored mucins in the goblet cells of the respiratory epithelium was measured. RESULTS: Drug dosage measurements showed that cyclosporine blood concentration at the moment the rats were killed was 1246.57 ± 563.88 ng/mL. The in vitro transport rate was significantly lower (P < .001) in the cyclosporin A-treated group. Also, the in-situ mucociliary transport rate was decreased in all cyclosporin A-treated animals when compared to the saline group (P = .02). Mucus quantity measurements showed a significant decrease on both acid (P = .01) and neutral (P = .02) mucus production from goblet cells in the animals submitted to cyclosporin A therapy. The correlation between the percentage of total mucus and in vitro transport rate was positive and significant (r = 0.706, P < .001), as was the correlation between the percentage of total mucus and the in situ mucociliary transport rate (r = 0.688, P = .001). CONCLUSION: This study shows that cyclosporin A plays an important role in the impairment of the mucociliary clearance in rats by reducing both acid and neutral mucus production from goblet cells and causing a decrease in the mucociliary transport velocity.

Prevalência de refluxo gastroesofágico em pacientes com doença pulmonar avançada candidatos a transplante pulmonar

“…(11) Furthermore, other factors have been experimentally described as contributing to the decrease in mucociliary transport velocity, such as bronchial transection and the use of cyclosporin A, both of which are common denominators in lung transplantation. (15,16) In the present study, we investigated the prevalence of GER and manometric abnormalities in a population of lung transplant candidates with advanced lung disease in an attempt to later make it possible to evaluate the impact of GER on the late performance of the post-lung transplant graft. In the population studied, the prevalence of pathological acid GER was 23%, somewhat lower than those reported in the literature-32% (14) and 35% (5) , which might be due to the small sample evaluated in our study.…”

Efeitos da azatioprina sobre a depuração mucociliar após secção e anastomose brônquica em um modelo experimental em ratos

“…(15) Other authors have studied, in other animal species, the effects of bronchial denervation on the mucociliary system and observed a decrease in MCT velocity. (16,17) Bronchial devascularization might have the additional effect of severely impairing MCT velocity. The principal hypothesis is that the reversibility of MCT impairment is due to vascular neoformation (revascularization of the bronchial tree), since bronchial anastomosis does not lead to recovery of the nerves.…”

Avaliação morfo-funcional do sistema mucociliar de traquéia de rato submetida a diferentes métodos de preservação em modelo de isquemia experimental

“…Uma dessas funções, a depuração mucociliar, se mantem mesmo após a retirada do enxerto (Pazetti et al, 2007). Portanto, a avaliação morfológica e funcional do enxerto traqueal antes do implante seria não só possível como necessária.…”

“…A avaliação da presença de muco ácido e neutro no epitélio respiratório foi realizada de forma quantitativa, por um programa de computador analisador de imagens, conforme descrito por Pazetti et al(2007). O programa avaliou a presença de muco pela quantificação da área de epitélio corada pelo azul de alcião e PAS.…”

“…O programa avaliou a presença de muco pela quantificação da área de epitélio corada pelo azul de alcião e PAS. Pazetti et al (2007) realizaram a quantificação em 10 campos com aumento final de 400 vezes para cada lâmina. Em nosso estudo, a análise foi realizada pela quantificação em apenas 01 campo com aumento final de 400 vezes para cada lâmina.…”