SONIA DE FATIMA SOTO YOSHIDA
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury(2016) ALMEIDA, Francine Maria; OLIVEIRA-JUNIOR, Manoel Carneiro; SOUZA, Renato Aparecido; PETRONI, Ricardo Costa; SOTO, Sonia Fatima; SORIANO, Francisco Garcia; CARVALHO, Paulo Tarso Camillo de; ALBERTINI, Regiane; DAMACENO-RODRIGUES, Nilsa Regina; LOPES, Fernanda Degobbi Tenorio Quirino Santos; CASTRO-FARIA-NETO, Hugo Caire; MARTINS, Milton Arruda; DOLHNIKOFF, Marisa; PAZETTI, Rogerio; VIEIRA, Rodolfo PaulaBACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage This study evaluated the effects of Cr supplementation in a model of lung PR. METHODS: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response. RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleulcin-1 beta (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001). CONCLUSIONS: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and antioxidant properties of Cr and modulation of TLRs.
conferenceObject Tacrolimus Causes Airway Mucociliary Clearance Impairment(2013) SILVA, M. P.; SOTO, S. F.; LIMONETE, T. T. K.; ALMEIDA, F. M.; JATENE, F. B.; PEGO-FERNANDES, P. M.; PAZETTI, R.Purpose: According to ISHLT Registry, the vast majority of lung transplant patients receive a tacrolimus-based maintenance immuno-suppressant therapy. However, its side effects on respiratory tract are not very well studied. We hypothesized that tacrolimus could impair airway mucociliary clearance. Methods and Materials: Twenty Wistar rats were assigned into two groups: Control (n¼10): saline solution; and TAC (n=10): tacrolimus (1 mg/kg/day). After 15 days of therapy by gavage, animals were killed and in situ mucociliary transport velocity (MCTV) and ciliary beating frequency (CBF) were measured by microscopic direct view of airway ciliated epithelium. Mucus production by goblet cells was quantified in periodic acid Schiff and alcian blue stained slides of the tracheobron-chial tissue. This study was support by São Paulo Research Foundation - Fapesp. Results: There was a significant decrease in MCTV (1.77 ± 0.50 and 0.73 ± 0.34 mm/min, Control and TAC, respectively, p<0.001) and CBF (15.06 ± 1.31 and 13.17 ± 1.47 Hertz, Control and TAC, respectively, p<0.001) in all TAC-treated animals. Indeed, tacrolimus caused an over production of mucus from airway goblet cells (12.78 ± 6.92 and 21.27 ± 7.86%, Control and TAC, respectively; p=0.007). Conclusions: Our study showed that TAC plays an important role on the impairment of the mucociliary clearance either by decreasing CBF and MCTV or by increasing mucus production. This impairment can be related with the high level of respiratory infection observed during the first 30 days after lung transplantation and must receive good attention from clinicians.