Hyperbaric oxygen attenuates cell growth in skin fibroblasts cultured in a high‐glucose medium

Abstract

Hyperglycemia and hypoxia synergistically retard diabetic wound healing. We investigated the direct effect of hyperbaric and normobaric hyperoxia on skin fibroblasts cultured in a high-glucose medium. Detroit 551 human dermal fibroblasts cultured in Dulbecco's modified Eagle's medium containing d-glucose had reduced cell survival compared with cells grown in normal glucose medium; survival was 27.5+/-3.8% lower in 25 mM glucose and 30.6+/-3.7% lower in 50 mM glucose. Cell survival decreased because of inhibition of cell proliferation and enhanced cell death. Daily hyperbaric oxygen therapy at 2.5 atmosphere absolute for 90 minutes on 3 consecutive days reduced cell proliferation and increased cell death in normal cultured fibroblasts. Hyperbaric oxygen therapy and high-glucose medium had a synergistic effect and reduced survival by 37.6+/-4.4% (25 mM glucose) and 39.6+/-5.1% (50 mM glucose). The effects of hyperbaric oxygen and high-glucose medium were associated with overproduction of reactive oxygen species. Our results suggest that direct exposure of skin fibroblasts to hyperbaric oxygen affects cell growth and superimposes the toxic effect of high glucose. This cytotoxicity may be related to the production of reactive oxygen species in the fibroblasts.

Mathematical Model of Hyperbaric Oxygen Therapy Applied to Chronic Diabetic Wounds

“…Decreased fibroblast proliferation. While it has been reported that the rate at which diabetic fibroblasts proliferate is not significantly lower than that of normal fibroblasts (Lerman et al, 2003), some authors claim that delayed and decreased fibroblast proliferation is a characteristic feature of nonhealing wounds (Moore et al, 1997;Enoch and Price, 2004;Lin et al, 2008). In Eq.…”

“…Oyibo et al (2001) state that the outcome of diabetic foot ulcers is influenced by (at least) blood supply and the presence of infection. An adequate oxygen supply is essential for healing and an inadequate oxygen supply is often reported as a cause of wound chronicity (Hunt et al, 1967(Hunt et al, , 1969Sen et al, 2002;Said et al, 2005;Hopf et al, 2006;Lin et al, 2008). We model decreased oxygen supply by reducing the parameter λ 5 in Eq.…”

“…Fibroblast proliferation has been observed to increase with increasing oxygen levels (Kessler et al, 2003;Lin et al, 2008) and so we employ a proliferation rate, λ 16 c c 0 +c , which is an increasing, saturating function of oxygen. Fibroblasts die (Clark, 1996) and we assume that their death rate is given by,…”

In silicodesign of treatment strategies in wound healing and bone fracture healing

“…For example, hyperbaric oxygen treatment at 3 atm roughly triples the oxygen diffusion between the capillaries and tissue (Grolman et al 2001). However, the increased level of oxygen also creates the risk of oxygen toxicity, but the effects can be minimized if the oxygen is breathed intermittently for 60-120 min (Lin et al 2008). Topical oxygen also has the advantages of using a portable device, being less expensive and delivering oxygen directly to the wound without the dependence of a vascular network (unless hyperbaric oxygen is delivered in a monoplace chamber).…”

“…The increased pressure (in contrast to normobaric treatment) creates a steeper pressure gradient, which helps the supplemental oxygen reach the cells (Lin et al 2008). For example, hyperbaric oxygen treatment at 3 atm roughly triples the oxygen diffusion between the capillaries and tissue (Grolman et al 2001).…”