Modulation of Hypoxia‐Induced Pulmonary Vascular Leakage in Rats by Seabuckthorn (Hippophae rhamnoides L.)

Jayamurthy Purushothaman,Rajesh Kumar,Himani Jayamurthy,Geetha Suryakumar,Ramesh Chand Sawhney,Dhananjay Shukla,Harinath Kasiganesan

doi:10.1093/ecam/nep199

Abstract

Cerebral and pulmonary syndromes may develop in unacclimatized individuals shortly after ascent to high altitude resulting in high altitude illness, which may occur due to extravasation of fluid from intra to extravascular space in the brain, lungs and peripheral tissues. The objective of the present study was to evaluate the potential of seabuckthorn (SBT) (Hippophae rhamnoides L.) leaf extract (LE) in curtailing hypoxia-induced transvascular permeability in the lungs by measuring lung water content, leakage of fluorescein dye into the lungs and further confirmation by quantitation of albumin and protein in the bronchoalveolar lavage fluid (BALF). Exposure of rats to hypoxia caused a significant increase in the transvascular leakage in the lungs. The SBT LE treated animals showed a significant decrease in hypoxia-induced vascular permeability evidenced by decreased water content and fluorescein leakage in the lungs and decreased albumin and protein content in the BALF. The SBT extract was also able to significantly attenuate hypoxia-induced increase in the levels of proinflammatory cytokines and decrease hypoxia-induced oxidative stress by stabilizing the levels of reduced glutathione and antioxidant enzymes. Pretreatment of the extract also resulted in a significant decrease in the circulatory catecholamines and significant increase in the vasorelaxation of the pulmonary arterial rings as compared with the controls. Further, the extract significantly attenuated hypoxia-induced increase in the VEGF levels in the plasma, BALF (ELISA) and lungs (immunohistochemistry). These observations suggest that SBT LE is able to provide significant protection against hypoxia-induced pulmonary vascular leakage.

Highlights

Acute exposure to hypoxia or high altitude induces a variety of illnesses like acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE)
The results from the present study suggest that SBT leaf extract (LE) is able to enhance hypoxic tolerance in experimental animals subjected to simulated hypobaric hypoxic stress
Administration of SBT LE caused a marked decline in transvascular fluid leakage into the lungs besides curtailing leakage of proteins and albumin into the alveoli and decreasing the proinflammatory markers in the lung

Summary

Introduction

Acute exposure to hypoxia or high altitude induces a variety of illnesses like acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Pulmonary hypertension, increased pulmonary capillary pressure and enhanced vascular permeability are the major factors for the development of HAPE [2, 3]. Hypoxia-induced oxidative stress plays a key role for the development of pulmonary hypertension and vascular leakage [4]. Earlier study by Bakonyi and Radak (2004) indicates that increased generation of reactive oxygen and nitrogen species may be responsible for hypoxia-induced increase in vascular permeability, which in turn may increase oxidative damage of lipids, proteins and DNA, besides decreasing the activity and effectiveness of the antioxidant enzyme system [5]. Supplementation with antioxidants may provide protection against hypoxia-induced oxidative stress and curtail high-altitude-induced maladies

Objectives

Methods

Conclusion