Suppressive activity of fexofenadine hydrochloride on nitric oxide production in-vitro and in-vivo

Abstract

The aim of this study was to examine the effect of fexofenadine hydrochloride (FEX), a histamine H1-receptor antagonist, on nitric oxide (NO) production in-vitro and in-vivo. Nasal fibroblasts (5 x 10(5) cells per mL) were stimulated with 25 ng mL(-1) tumour necrosis factor-alpha in the presence of various concentrations of FEX. NO levels in 24-h-culture supernatants were measured by the Griess method and levels of inducible nitric oxide synthase (iNOS) mRNA levels in 12-h-cultured cells were measured by ELISA. FEX at more than 0.5 microg mL(-1) suppressed NO production from fibroblasts by inhibiting expression of iNOS mRNA. We also examined whether FEX could suppress NO production induced by lipopolysaccharide (LPS) stimulation in-vivo. BALB/c mice were treated with 5.0 mg kg(-1) LPS i.p. after daily oral doses of FEX, 1.0 mg kg(-1), for 1-3 weeks. Plasma was obtained 6 h later and NO levels measured by the Griess method. Expression of iNOS mRNA in lung tissues was measured by ELISA 6 h after LPS injection. Oral administration of FEX for 2 and 3 weeks, but not 1 week, significantly suppressed NO levels in plasma through the inhibition of iNOS mRNA expression, which were enhanced by LPS stimulation. These results suggest that the attenuating effect of FEX on NO production may be of therapeutic benefit in allergic diseases.

Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro

“…The residual cells were stimulated with LPS in the presence of various concentrations of agents in a total volume of 2.0 ml. To prepare culture supernatants, cells were cultured for 24 hours [ 21 ], and the culture medium was removed and stored at -40°C until used. Cells for examination of phosphorylation of mitogen-activated protein kinases (MAPKs), transcription factor activation, inducible NO synthase (iNOS) mRNA expression and iNOS protein were cultured in a similar manner for 2, 4, 8 and 12 hours, respectively.…”

Nasal nitric oxide and its metabolites as potential biomarkers for the diagnosis and follow-up of allergic rhinitis

“…It was also shown that fexofenadine suppressed NO production in nasal fibroblasts in vitro and in lung tissue of rats in vivo. [27] Takeno et al showed that increased nasal NO levels in AR patients were caused by increased levels of the iNOS isoenzyme form. [28] Kawamoto et al compared iNOS levels of various nasal tissues of patients with AR and the control group.…”

Assessment of antihistamines in the treatment of skin allergies

“…( Table 3). Interestingly, it has been reported that antihistamines have favorable pharmacological properties on these aspects in vitro [2, [29][30][31][32][33][34][39][40][41][42][43][44][45][46]. Keratinocytes are considered an immunocompetent cell type for the production of cytokines or other biological substances.…”