Modulative effect of new hydrazide derivative on wheat induced pulmonary inflammation in rats.

NEW FINDINGS: What is the central question of this study? Pulmonary inflammation is associated with asthma, wheat and thresher dust contributed to pulmonary inflammation when exposed/inhaled regularly as by bakers and farmers. Mechanisms through which wheat induced pulmonary inflammation and how the hydrazide derivative exerts its modulative anti-inflammatory effect have not been previously explored. What is the main finding and its importance? 10 mg/Kg of hydrazide derivative exhibited significant reduction in wheat induced pulmonary inflammation rat model mainly by down-regulating the inflammatory cell infiltration, pathological lesions in the lungs and the level of pro-inflammatory cytokines, COX-1, COX-2 and T-cell proliferation.

ABSTRACT: Presently, we investigated the ameliorative anti-inflammatory effect of previously synthesized hydrazide derivative (MD) as an immunomodulator in newly developed allergen induced pulmonary inflammation (AIPI) rat model. Wheat and thresher dust was used as allergens to induce pulmonary inflammation while MD was used to reverse the inflammatory response. Blood and Bronchoalveolar Lavage Fluid (BALF) were collected post sacrificing the rats and inflammatory cells were counted. Histological analysis of lung airways was carried out by HE and PAS staining while the level of total serum IgE, IL-4, IL-5, COX-1 in BALF and in vitro T-cell proliferation in spleen was measured through ELISA. mRNA expression level of IL-4, IL-5, IL-13, TGF-β, IFN-γ, TNF-α, COX-1 and COX-2 was evaluated by qRT-PCR. Liver and kidney function test was assessed to observe any toxic impact of MD. Results indicated that 2 mg of wheat and thresher dust exhibited higher levels of inflammatory cytokines in the blood, BALF and lung airways of rats. MD potentially down-regulated the inflammatory cell infiltration in BALF and pathological lesions in the lung airways of AIPI rats. MD significantly suppressed the elevated total serum IgE, along with IL-4, IL-5, IL-13, TGF-β, COX-1, COX-2 mRNA expression and T-cell proliferation in spleen. In conclusion, MD at 10 mg/Kg exhibited a significant reduction in all the markers in both, wheat and thresher dust induced pulmonary inflammation mainly by inhibiting the pro-inflammatory cytokines, and T-cell proliferation. The data suggests that inhibition of T-cell response may be responsible for modulative effect of MD in AIPI rat model. This article is protected by copyright. All rights reserved.