The applications

I – Context

The Exp'Air system has been under trial for 3 years at AR2i in conjunction with the Multidisciplinary Functional Testing Department of the Antoine Béclère Hospital in Clamart (Paris region).

The Exp'Air system is an original medical device enabling non-invasive and reproducible collection of the volatile substances contained in the alveolar fraction of expired air.

As a result of these trials, several hypotheses have seen the light regarding the role of certain halogenated alkanes, particularly chlorofluoroalkanes, in the regulatory mechanisms of oxidative stress.

The presence of chlorofluoroalkanes in expired air, trichlorotrifluoroethane in particular, has already been documented.

II – Trials

The increase in the proportion of chlorofluoroalkanes in the expired air was observed by chance in subjects placed under various conditions known to generate oxidative stress:

  • Moderate physical effort
  • Intense physical effort
  • Cigarette smoking
  • Mental effort
  • Apnoea

In each case studied, samples were taken before and after applying the stress factor.

The level of chlorofluoroalkanes (3 chemical species were detected) increased in proportion with the intensity of the stress applied (5 to 100 times the initial level). The response to the stress is very rapid (5 – 10 minutes) and short-lived: the levels return to normal within 30 minutes to 2 hours, depending on the intensity of the stress inflicted.

To date, the chemical species that have been identified are:

  • Trichlorotrifluoroethane
  • Dichlorodifluoromethane
  • Tetrafluoroethane

III – Interpretation

  • As with nitric oxide (NO), originally known as EDRF (Endothelial Derived Releasing Factor), the effects of the molecules were highlighted before the metabolic origin was determined. The endogenous origin of these chlorofluoroalkanes was confirmed through sampling and analysis under various environmental conditions.
  • The predominant species, trichlorofluoroethane (TCFE), was tested in vitro on the mitochondrial respiratory chain: this substance was shown to inhibit the respiratory chain.
  • It is known that halogenoalkanes play a role in redox mechanisms. Bromoalkanes and halons, in particular, are used as fire-extinguishers; they block the free radicals produced by the flame and thus reduce the amount of energy released and stop the fire from spreading.

Today, the following hypotheses exist:

  • Chlorofluoroalkanes are early markers of oxidative stress.
  • They are generated by the body in order to reduce the production of the free radicals responsible for oxidative stress damage (lipid peroxidation, cell and mitochondrial membrane lesions, attacks on DNA, etc.).
  • They act as "biological extinguishers", partly because they reduce the activity of the respiratory chain, and partly because they chemically block the oxygen free radicals (ROS), thus stopping the radical reaction.
  • Their action is short-lived and is evidence of "acute" oxidative stress. As an example, the increase in the level of chlorofluoroalkanes in the expired air after intense physical effort is explained as follows:

- An intense physical effort engenders both an increased need for oxygen and a rise in blood CO2 (hypercapnia), whence metabolic acidosis.
- It is known that the need for oxygen is outweighed by the need to eliminate CO2  to fight against acidosis: hyperventilation following physical effort is therefore a reflex mechanism intended to eliminate the CO2.
- As a consequence, the elimination of CO2 by means of hyperventilation is accompanied by an excess of oxygen caused by this very hyperventilation.
- The excess of oxygen tends to lead to over-activity of the mitochondrial respiratory chain which generates ROS and thus oxidative stress.
- It is therefore logical that the body should produce chlorofluoroalkanes in these conditions, since their action will reduce the effects of oxidative stress following intense physical effort.

  • Inversely, the more persistent, unhalogenated alkanes are biological markers of "chronic" and repeated stress, when the body's ability to resist reaches its capacity (continual or repeated stress, insufficient metabolic antioxidant potential).
  • In summary, if we were to compare oxidative stress to a fire, the chlorofluoroalkanes are the "fire extinguishers" and the alkanes are the "ashes" of the fire, since it is known that these compounds are produced by lipid peroxidation (the effects of the fire).

 

 

 
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