p-Coumaric acid as a prophylactic measure against normobaric hypoxia induced pulmonary edema in mice

Aims: Previous studies indicate that the anti-hypoxia effects of Tibetan Turnip (Brassica rapa ssp. rapa) were closely related to its characteristic components being p-coumaric acid (CA) and p-coumaric acid-beta-D-glucopyranoside (CAG). Since CAG would be converted to CA in vivo, this study aims to further examine the efficacy and mechanism of CA against pulmonary edema induced by normobaric hypoxia. Main methods: Male ICR mice were assigned to the normoxia group and several hypoxia groups, given sterile water, CA or dexamethasone orally, once daily for four consecutive days. One hour after the final gavage, mice in the above hypoxia groups were put into the normobaric hypoxia chamber (9.5% O-2) for 24 h while mice in normoxia group remained outside the chamber. After hypoxia exposure, lung water content (LWC), pulmonary vascular permeability, the protein content of bronchoalveolar lavage fluid (BALF), plasma total nitrate/nitrite (NOx) and endothelin-1 (ET-1) content, histological and ultra-microstructure analyses were performed. Expression of occludin was assayed by immunohistochemistry. Key findings: In a hypoxic environment of 9.5% O-2, mice treated with 100 mg/kg body wt CA had significantly lower LWC and BALF protein content than mice in the hypoxia vehicle group. Meanwhile, mice in CA group showed intact lung blood-gas-barrier, increased levels of plasma total NO, decreased levels of plasma ET-1 and upregulation of occludin expression. Significance: CA exerts preventive effects against normobaric hypoxic pulmonary edema in mice, its mechanisms involved improving the integrity of the lung barrier, inhibiting oxidative stress and inflammation.