Study On The Effect Of Rupatadine On Oleic Acid-induced Acute Lung Injury In Animals And On LPS-induced Rat Pulmonary Alveolar Macrophage Cell Line NR8383

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The pathogenesis of them is complicated and not well known. They have high mortality and no effective cure has been established. Rupatadine is a new agent for the management of disease with allergic inflammatory conditions, such as seasonal and perennial rhinitis. It is a potent dual antagonist of histamine and platelet-activating factor (PAF), possessing a unique profile as it combines both activities with a high level of potency. There were no reports about its effect on lung inflammation. In the present study, we established the ALI/ARDS animal models and investigated rupatadine's protect effect and mechanisms. In addition, we studied the intervene effect of rupatadine on lipopolysaccharide (LPS)-mediated inflammatory factors in pulmonary alveolar macrophage cell line NR8383.1. The protective effect of rupatadine on oleic acid-induced ALI in rabbitsRupatadine was given intravenously through ear margin with a sustaining infusion 30mins before OA injection. The OA-induced descent of arterial blood oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in bronchoalveolar lavage fluid (BALF) in rupatadine group. Furthermore, the changes in edema fluid accumulation in BLAF,wet/dry weight ratio,histopathology observation in the lung are all alleviated or attenuated by rupatadine administration.2. Effect of rupatadine on ALI induced by oleic acid in rats.Rupatadine was given before injection of oleic acid at dose of 10, 20, 40mg/kg. The changes of lung inspiratory resistance, expiratory resistance and dynamic lung compliance were real time recorded by anrise2005 pulmonary function test apparatus. Lung wet to dry weight ratio was calculated. The concentration of protein and TNF-αlevel in BALF were measured. Pretreatment of rupatadine significantly alleviated lung injury by improvement of lung function, reduction of lung wet to dry weight ratio and decreased the protein concentration, suppressed the increase of TNF-α. 3. The effect of rupatadine on LPS-induced rat pulmonary alveolar macrophage cell line NR8383NR8383 cells were pretreated with rupatadine, and then were stimulated with LPS. The production of TNF-αin the supernatant of NR8383 was detemined with enzyme-linked immunosorbent assay (ELISA). The TNFαmRNA level was determined by a semi-quantitative PCR assay. The findings indicated that rupatadine could inhibit LPS- stimulated TNFαmRNA expression and TNF-αproduction.In conclusion, our studies suggested that rupatadine has a dose-dependent beneficial effect on acute lung injury induced by oleic acid. In addition, rupatadine could inhibit LPS- induced mRNA expression and production of TNF-αin NR8383 cells. So we infer that rupatadine may have a protective effect on lung inflammatory through its inhibitory effect on synthesis of inflammatory factors.