Effects of xylene on respiratory mucosa in rats / Efectos del xileno sobre la mucosa respiratoria de ratas

In this study we examined the effects histopathologic and immunohistochemical of xylene inhalation in rats by using light microscopy. Adult wistar albino rats were used in this study. Eight rats were in control group and 8 rats were in the experimental group. The experimental group was exposed to 300 ppm formaldehyde 3­5 min/day, 5 days/week for 8 weeks. The lining epithelium of respiratory mucosa showed a loss of ciliated cells with metaplasia of goblet cells, hyperplasia of squamous cells and edema, inflamation in sub epithelial area). In the group treated xylene. Disruption of cell-cell contact was observed. Weak expression of E-cadherin was observed between cells. The vascular endothelium of capillaries and venoles showed intense immunostaining for VEGF.

Se examinó el efecto histopatológico e inmunohistoquímico de la inhalación de xileno en ratas mediante el uso de microscopía de luz. Se utilizaron ratas albinas Wistar adultas. Ocho ratas formaron parte del grupo control y 8 del grupo experimental. El grupo experimental fue expuesto a 300 ppm de formaldehído, 3­5 min/día, 5 días/semana, durante 8 semanas. El epitelio de revestimiento de la mucosa respiratoria mostró una pérdida de células ciliadas con metaplasia de células caliciformes, hiperplasia de células escamosas y edema, con inflamación en la zona subepitelial. En el grupo tratado con xileno se observó una interrupción del contacto célula-célula. Se observó una débil expresión de E-cadherina entre las células. El endotelio vascular de los capilares y vénulas mostraron intensa inmunotinción de VEGF.

The impact of topically applied preservation solutions on the respiratory epithelium of tracheal grafts submitted to cold ischemia: functional and morphological analysis

OBJECTIVE: Advances in graft reepithelialization and revascularization have renewed interest in airway transplantation. This study aims to determine whether topically applied preservation solutions can ameliorate ischemic injury to tracheal grafts. We analyzed 1) the effects of cold ischemia on the mucociliary clearance of tracheal grafts and 2) the impact of topically applied preservation solutions on the effects of cold ischemia on mucociliary clearance. METHOD: Tracheal segments (n=217) from 109 male Wistar rats were harvested, submerged in low-potassium-dextran-glucose, histidine-tryptophan-ketoglutarate, or saline solution (saline group), and stored at 4°C for 6, 10, 16, or 24 hours. A control group (not submerged) was analyzed immediately after harvesting. In situ mucociliary transport and ciliary beating frequency were measured using a stroboscope. Epithelial integrity, cellular infiltration, and mucus storage were quantified by light microscopy and image analysis software, along with transmission electron microscopy. RESULTS: 1) The effects of cold ischemia: in situ mucociliary transport and ciliary beating frequency were greater in the control group than after cold ischemia. Microscopic analysis results were similar between groups. 2) The effects of preservation solutions: there was no difference between the low-potassium-dextran-glucose, histidine-tryptophan-ketoglutarate, and saline groups in functional or light microscopy analysis. The saline group presented stronger signs of ischemic injury with transmission electron microscopy. CONCLUSIONS: Cold ischemia diminished the mucociliary clearance of the tracheal respiratory epithelium. Topically applied preservation solutions did not ameliorate the injury caused by cold ischemia to the tracheal respiratory epithelium. .

Ozone Exposure Suppresses Proliferative Response in Mice Skin

No abstract available.

Suppression of CFTR-mediated Cl- Secretion of Airway Epithelium in Vitamin C-deficient Mice

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.

Effects of Scutellarin on MUC5AC Mucin Production Induced by Human Neutrophil Elastase or Interleukin 13 on Airway Epithelial Cells

Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron breviscapus. The present study investigated the effect of scutellarin on MUC5AC mucin production and the possible mechanism. Human bronchial epithelial 16 (HBE16) cells were pretreated with scutellarin for 60 min, and then exposed to human neutrophil elastase (HNE) or interleukin (IL)-13 for 12 hr. RT-PCR and ELISA were performed to measure the amount of MUC5AC mucin production. The results showed that scutellarin inhibited MUC5AC expression both in mRNA and protein level induced by HNE in a concentration-dependent manner. However, scutellarin failed to inhibit MUC5AC mucin production induced by IL-13. To investigate the intracellular mechanisms associated with the effect of scutellarin on MUC5AC mucin production, western blotting was carried out to examine the phosphorylation of protein kinase C (PKC), signal transducer and activator of transcription 6 (STAT6) and extracellular signal-regulated kinase 1/2 (ERK1/2). The phosphorylation of PKC and ERK1/2 was attenuated after treatment with scutellarin, whereas STAT6 was not significantly affected. Therefore, it is suggested that scutellarin down-regulates MUC5AC mucin production on HBE16 cells via ERK-dependent and PKC-dependent pathways.

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.