Evidence of cell damages caused by circulating bubbles: high level of free mitochondrial DNA in plasma of rats.
Bubble formation can occur in the vascular system after diving, leading to decompression sickness (DCS). DCS signs and symptoms range from minor to death. Too often, patients are admitted to a hyperbaric center with atypical symptoms, as bubbles cannot be detected anymore. In the absence of a relevant biomarker for humans, the therapeutic management remains difficult. As circulating DNA was found in the blood of healthy humans and animals, our study was made to correlate the extracellular mitochondrial DNA (mDNA) concentration with the occurrence of clinical DCS symptoms resulting from initial bubble-induced damages. Therefore, 109 rats were subjected to decompression from a simulated 90-m sea water dive, after which, 78 rats survived (71.6%). Among the survivors, 15.6% exhibited typical DCS symptoms (DCS group), whereas the remaining 56% showed no detectable symptoms (noDCS group). Here, we report that the symptomatic rats displayed both a circulating mDNA level (DNADCS → 2.99 ± 2.62) and a bubble grade (median Spencer score = 3) higher than rats from the noDCS group (DNAnoDCS → 1.49 ± 1.27; Spencer score = 1). These higher levels could be correlated with the platelet and leukocyte consumption induced by the pathogenic decompression. Rats with no detectable bubble had lower circulating mDNA than those with higher bubble scores. We determined that in rats, a level of circulating mDNA >1.91 was highly predictive of DCS with a positive-predictive value of 87.3% and an odds ratio of 4.57. Thus circulating mDNA could become a relevant biomarker to diagnose DCS and should be investigated further to confirm its potential application in humans.
Equipe Résidante de Recherche Subaquatique Opérationnelle, Institut de Recherche Biomédicale des Armées, Toulon, Département Environnement Opérationnel, Unité Environnements Extrêmes, Toulon Cedex, France.
Nicolas
N
Vallée
Sandrine
S
Gaillard
André
A
Peinnequin
Jean-Jacques
JJ
Risso
Jean-Eric
JE
Blatteau
D000818:Animals; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000097:blood*; D003664:Decompression / Q000009:adverse effects*; D003665:Decompression Sickness / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004242:Diving; D004906:Erythrocyte Count; D005740:Gases / Q000097:blood; D005819:Genetic Markers; D007958:Leukocyte Count; D008297:Male; D016017:Odds Ratio; D010976:Platelet Count; D011237:Predictive Value of Tests; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley
D004272:DNA, Mitochondrial; D005740:Gases; D005819:Genetic Markers
biomarker; bubble; diving; gas; nitrogen