Biomedical subjects

Vincent Castranova

Publications and source records attributed to Vincent Castranova.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Pharmacological studies of the effect of wheat grain extract.

BACKGROUND: Agricultural farm workers exposed to wheat grain dust are at risk of developing respiratory abnormalities. The pathogenesis of this injury is only partially understood. OBJECTIVES: To determine the effect of wheat grainextract on isolated guinea pig tracheal smooth muscle. METHODS: In the current study, pharmacologic properties of wheat grain extract (WGE) were tested using guinea pig tracheas studied in vitro. Dose-related contractions of nonsensitized guinea pig trachea were demonstrated using these extracts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth muscle contraction: atropine 10(-6)M, indomethacin 10(-6)M, pyrilamine 10(-6)M, acivicin 10(-5)M, nordihydroguaretic acid (NDGA) 10(-5)M, bromophenacyl bromide (BPB) 10(-5 )M, 3,4,5-trimethoxybenzoic acid-8-(diethylamino)- octyl ester TMB8 10(-5)M, captopril 10(-5)M and capsaicin 5 x 10(-6)M. RESULTS: WGE causes a dose-dependent constriction of guinea pig tracheal smooth muscle. Atropine, pyrilamine, TMB8 and acivicin significantly reduced the contractile effects of the WGE. Inhibition of contraction by blocking of other mediators was significant but less complete. CONCLUSION: We conclude that WGE causes a dose-related constriction of airway smooth muscle by nonimmunological mechanisms involving a variety of airway mediators and possibly cholinergic receptors.

Animals↗

PubMedDate not supplied

Involvement of hydrogen peroxide in asbestos-induced NFAT activation.

The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by asbestos in mouse embryo fibroblast PW cells. Exposure of cells to asbestos led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of asbestos-induced H2O2 with N-acety-L-cyteine (NAC, a general antioxidant) or catalase (a specific H2O2 inhibitor) resulted in inhibition of NFAT activation. In contrast, an increase in H2O2 generation by the addition of superoxide dismutase (SOD) slightly enhanced asbestos-induced NFAT activation. In addition, pretreatment of cells with sodium formate did not exhibit any inhibition of NFAT activity induced by asbestos. These results demonstrated that H2O2 appeared to play an important role in asbestos-induced NFAT transactivation. Furthermore, it was observed that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) not only resulted in NFAT activation by itself, but also enhanced asbestos-induced NFAT induction. Pretreatment of cells with cyclosporin A (CSA), a pharmacological inhibitor of the phosphatase calcineurin, blocked both asbestos- and TPA plus asbestos-induced NFAT activation. These data suggest that asbestos is able to induce NFAT activation through H2O2-dependent and CSA-sensitive pathways, which may be involved in asbestos-induced carcinogenesis.

Acetylcysteine↗

PubMedDate not supplied

Effect of inhaled crystalline silica in a rat model: time course of pulmonary reactions.

Numerous investigations have been conducted to elucidate mechanisms involved in the initiation and progression of silicosis. However, most of these studies involved bolus exposure of rats to silica, i.e. intratracheal instillation or a short duration inhalation exposure to a high dose of silica. Therefore, the question of pulmonary overload has been an issue in these studies. The objective of the current investigation was to monitor the time course of pulmonary reactions of rats exposed by inhalation to a non-overload level of crystalline silica. To accomplish this, rats were exposed to 15 mg/m3 silica, 6 h/day, 5 days/week for up to 116 days of exposure. At various times (5-116 days exposure), animals were sacrificed and silica lung burden, lung damage, inflammation, NF-KB activation, reactive oxygen species and nitric oxide production, cytokine production, alveolar type II epithelial cell activity, and fibrosis were monitored. Activation of NF-KB/DNA binding in BAL cells was evident after 5 days of silica inhalation and increased linearly with continued exposure. Parameters of pulmonary damage, inflammation and alveolar type II epithelial cell activity rapidly increased to a significantly elevated but stable new level through the first 41 days of exposure and increased at a steep rate thereafter. Pulmonary fibrosis was measurable only after this explosive rise in lung damage and inflammation, as was the steep increase in TNF-alpha and IL-1 production from BAL cells and the dramatic rise in lavageable alveolar macrophages. Indicators of oxidant stress and pulmonary production of nitric oxide exhibited a time course which was similar to that for lung damage and inflammation with the steep rise correlating with initiation of pulmonary fibrosis. Staining for iNOS and nitrotyrosine was localized in granulomatous regions of the lung and bronchial associated lymphoid tissue. Therefore, these data demonstrate that the generation of oxidants and nitric oxide, in particular, is temporally and anatomically associated with the development of lung damage, inflammation, granulomas and fibrosis. This suggests an important role for nitric oxide in the initiation of silicosis.

Administration, Inhalation↗

PubMedDate not supplied

Differential role of hydrogen peroxide in UV-induced signal transduction.

The present study investigated the differential requirement of ROS in UV-induced activation of these pathways. Exposure of the mouse epidermal C141 cells to UV radiation led to generation of ROS as measured by electron spin resonance (ESR) and by H2O2 and O2. fluorescence staining assay. Treatment of cells with UV radiation or H2O2 also markedly activated Erks, JNKs, p38 kinase and led to increases in phosphorylation of Akt and p70(S6k) in mouse epidermal JB6 cells. The scavenging of UV-generated H2O2 by N-acety-L-cyteine (NAC, a general antioxidant) or catalase (a specific H2O2 inhibitor) inhibited UV-induced activation of JNKs, p38 kinase, Akt and p70(S6k), while it did not show any inhibitory effects on Erks activation. Further, pretreatment of cells with sodium formate (an .OH radical scavenger) or superoxide dismutase (O2-. radical scavenger) did not inhibit any of these pathways. These results demonstrate that H2O2 generation is required for UV-induced phosphorylation of Akt and p70(S6k), and involved in activation of JNKs and p38 kinase, but not Erks.

Animals↗