Effects of hyperbaric oxygen on oxidative stress, angiogenesis factors and endothelial cell injury

  • Jianfeng Yuan

Student thesis: PhD

Abstract

Hyperbaric oxygen (HBO) therapy is the administration of 100% oxygen at more than one atmosphere. It greatly improves tissue oxygenation and facilitates mechanisms of wound healing, which in turn benefits some patients with chronic wounds. A prominent fact in therapeutic HBO is the acceleration of neoangiogenesis during granulation tissue formation. Angiogenesis is a highly orchestrated event, a diverse range of cells and angiogenesis factors are involved in the process. The formation of reactive oxidative species (ROS) during HBO has been controversially considered as signalling regulator for angiogenic factors, as well as harmful originator for oxidative stress-induced cyto- and geno-toxicity in cells. This thesis contributes to this interesting while challenging topic. The project starts with investigation the direct HBO effects on blood vessel in vitro under physiological conditions and pathological conditions. The data clearly show that a single HBO treatment does not induce oxidative stress and cell damage under physiological conditions. Nevertheless, under pathological conditions, HBO induces oxidative stress with more ROS formation and cell damage. Interestingly, no evidence has been shown that HBO alone or synergically promotes nitric oxide and vascular endothelial growth factor production in either condition. The response of blood vessel to HBO treatment is not explained by autocrine release of angiogenesis factors locally in the blood vessel. Next, HBO-induced intracellular calcium (Ca2+) changes and DNA damage were investigated using cultured human umbilical vein endothelial cells. A single HBO treatment significantly elevates intracellular Ca2+ level without inducing cell damage. Furthermore, HBO treatment has small but significant effect on DNA migration when evaluated by comet assay (e.g. 6.8 ± 0.8 % comparing to 4.6 ± 0.2 % DNA in tail of air treatment). However, this effect is totally reversible after 24h recovery. Importantly, HBO treatment protects endothelial cells against subsequent oxidative stress attack, and an increased antioxidant capacity was found as reflected in higher ratio of GSH to GSSG. The findings suggest that the beneficial effect of HBO is possibly via HBO-induced adaptation in cellular redox status. However, the details of Ca2+ signalling and roles of antioxidants in HBO treatment are areas for further research.
Date of Award2007
Original languageEnglish
Awarding Institution
  • University of Plymouth

Keywords

  • Hyperbaric Oxygen
  • Oxidative Stress
  • Vascular Endothelial Growth Factor
  • Nitric Oxide
  • Endothelial Cells
  • Calcium
  • DNA Damage

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