OBJECTIVETo investigate the effect of spearmint oil on emphysema-like changes and the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta(IL-1beta), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-9) in lipopolysaccharide (LPS) treated rats.

METHODEmphysematous changes model was induced by intratracheal instillation of LPS once a week for up to 8 weeks in rats. Rats were divided into control, dexamethasone (0.3 mg x kg(-1)), and spearmint oil (10, 30,100 mg x kg(-1)) groups. Each group was treated with saline, dexamethasone, and spearmint of oil respectively for 4 weeks. Then total and different white blood cell counts in bronchoalveolar lavage fluid(BALF) were carried out. The pathologic changes of lung tissue such as alveolar structure, airway inflammation, and goblet cell metaplasia were observed by HE and AB-PAS staining. Expression of TNF-alpha, IL-1beta, TIMP-1 and MMP-9 were measured.

RESULTBoth spearmint and dexamethasone decreased the destruction of pulmonary alveolus. The total and different white blood cell counts in BALF including neutrophile and lymphocyte of spearmint oil 100 mg x kg(-1) and dexamethasone group were significantly reduced, and the goblet cell metaplasia was also inhibited. Dexamethasone had inhibitory effect on the expression of TNF-alpha, IL-1beta, TIMP-1 and MMP-9. Spearmint oil 30, 100 mg x kg(-1) significantly reduced TNF-alpha and IL-1beta respectively. Spearmint oil 10, 30 and 100 mg x kg(-1) had no effect on the expression of TIMP-1, but could decrease the expression of MMP-9 significantly in lung tissues.

CONCLUSIONSpearmint oil has protective effect on rats with emphysematous changes, since it improves alveolar destruction, pulmonary inflammation, and goblet cell metaplasia. The mechanism may include reducing TNF-alpha, IL-1beta content and inhibiting overexpression of matrix metalloproteinase-9 in lung tissues.

Animals ; Azo Compounds ; pharmacology ; Bronchoalveolar Lavage Fluid ; cytology ; Goblet Cells ; drug effects ; Interleukin-1beta ; drug effects ; metabolism ; Leukocytes ; drug effects ; metabolism ; Lipopolysaccharides ; Lymphocytes ; drug effects ; metabolism ; Matrix Metalloproteinase 9 ; drug effects ; metabolism ; Mentha spicata ; chemistry ; Metaplasia ; Monocytes ; drug effects ; metabolism ; Neutrophils ; drug effects ; metabolism ; Phytotherapy ; Plant Oils ; therapeutic use ; Pulmonary Emphysema ; chemically induced ; drug therapy ; enzymology ; pathology ; Rats ; Respiratory System ; drug effects ; pathology ; Tissue Inhibitor of Metalloproteinase-1 ; drug effects ; metabolism ; Tumor Necrosis Factor-alpha ; drug effects ; metabolism

PURPOSE: To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. RESULTS: There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. CONCLUSIONS: The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
Animals ; Conjunctiva/*drug effects/pathology ; Cornea/metabolism ; Disease Models, Animal ; Drug Combinations ; Dry Eye Syndromes/*drug therapy/metabolism ; Emollients/administration & dosage ; Female ; Goblet Cells/drug effects/metabolism/pathology ; Hyaluronic Acid/*administration & dosage ; Mice ; Mice, Inbred C57BL ; Mineral Oil/*administration & dosage ; Ophthalmic Solutions ; Tears/*metabolism ; Viscosupplements/administration & dosage

PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA) on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6 seconds), were treated with topical application of CS-HA on one eye and CsA on the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia, and conjunctival impression cytology (CIC; goblet cell density, nucleus to cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared between eyes before and after treatment (repeated measurement of ANOVA). RESULTS: After treatment, BUT and tear wettings were significantly prolonged in each group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was no significant difference in tear wetting (p=0.132). While the 3 parameters of CIC improved in both groups, goblet cell density was significantly higher in eyes treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops improve ocular surfaces, topical CsA may have a better effect on enhancing tear film stability and goblet cell density.
Adjuvants, Immunologic/administration & dosage ; Administration, Topical ; Cell Count ; Chondroitin Sulfates/*administration & dosage ; Conjunctiva/drug effects/pathology ; Cyclosporine/*administration & dosage ; Drug Administration Schedule ; Drug Combinations ; Drug Therapy, Combination ; Dry Eye Syndromes/*drug therapy/metabolism/pathology ; Epithelium/drug effects/pathology ; Female ; Follow-Up Studies ; Goblet Cells/drug effects/pathology ; Humans ; Hyaluronic Acid/*administration & dosage ; Immunosuppressive Agents/*administration & dosage ; Male ; Middle Aged ; Ophthalmic Solutions/administration & dosage ; Tears/drug effects/metabolism ; Time Factors ; Treatment Outcome

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.
Animals ; Antineoplastic Agents/*therapeutic use ; Bronchoalveolar Lavage Fluid/cytology ; Cytokines/biosynthesis ; Enzyme Activation ; Eosinophils/cytology ; Goblet Cells/pathology ; Inflammation/drug therapy/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/*therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/metabolism ; Respiratory Hypersensitivity/*drug therapy/etiology/metabolism ; Respiratory Mucosa/drug effects/pathology