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Investigations on the respiratory effects of ozone in the rodent / Cornelius Jacon Lotriet

Ozone, being an unstable molecule, is believed to be one of the strongest oxidant
agents known to man. Rapid growth in the application of ozone — both as
disinfectant and as form of alternative medicine — led to questions about the effects
of uncontrolled ozone exposure and inhalation, whether intentional or unintentional,
on the human body.
This study specifically focussed on examining, identifying and substantiating the
respiratory effect of acute exposure (10 min or less) to considerably higher ozone
concentrations than reported on before (19.5 ± 0.5 ppm). Respiratory tissue of
rodents (Duncan–Hartley guinea pigs of both sexes and Male Wistar rats) was
subjected to ozone by utilising three distinctly diverse models of ozone introduction:
(a) in vitro exposure, (b) in vivo exposure, and (c) ex vivo by employing an isolated
lung perfusion model which allows for real–time, breath–by–breath data acquisition of
ozone’s effect on respiratory mechanics. The effect of ozone on the isolated trachea
in the presence of various drugs with well–known effects, including methacholine,
isoproterenol and ascorbic acid was also examined.
The results found in this study identified two direct effects on the isolated trachea due
to ozone exposure: (1) a definite contraction of the isolated trachea immediately after
exposure to ozone, and (2) a clearly visible and significant hyper responsiveness of
the isolated trachea to irritants, e.g. methacholine. Although ozone has a negative
effect on the trachea, it was concluded that ozone has no adverse effect on
muscarinic acetylcholine receptors. An apparent EC50 value of ozone on the trachea
was established by two different methods as (2.77 ± 0.02) x 10–3 M and (2.10 ± 0.03)
x 10–3 M, respectively. Ozone furthermore displayed an attenuation of the beneficial pharmacological
response of –sympathomimetic drugs (i.e. isoproterenol), while isoproterenol itself
has a relaxing effect on the ozone–induced contraction of the isolated trachea.
Indomethacin pre–treatment of isolated tracheal tissue significantly (77%) reduced
the ozone–induced contraction of tracheal smooth muscle, suggesting that COXproducts
of arachidonic acid play a prominent role in the development of pulmonary
function decrements consequent to acute high–dose ozone exposure. Ascorbic acid
exhibited a meaningful prophylactic effect on ozone–induced contraction of both
isolated tracheal tissue and in the isolated lung perfusion model, emphasising the
major role antioxidants play in both the epithelium lining fluid (ELF) of the respiratory
system and in plasma throughout the body in protecting against the destructive
effects of ozone.
Surprisingly, pre–treatment with ascorbic acid did not prevent hyper responsiveness
of isolated tracheal preparations to methacholine after a 10 min ozone (19.5 ± 0.5
ppm) exposure. In the lung perfusion model, the presence of ascorbic acid in the
perfusion medium did, however, significantly reduce the magnitude and rate of
decline in lung compliance after ozone exposure (46% decline with ascorbic acid
versus 96% in the control study without ascorbic acid).
Examination of a lung perfusion model exposed to ozone (19.5 ± 0.5 ppm O3; 5
seconds) presented a significant decline in lung compliance (95.6% within 2 min),
tidal volume (70%) and maximum inspiratory flow (71.2%), with an ensuing reduction
in lung elasticity and severely hampered breathing pattern.
Microscopic examination after acute high–dose inhalation studies did not display any
significant cellular damage, oedema or inflammation after acute high–dose ozone
exposure. This suggests that significant cellular injury and inflammation is possibly
not the causative factor of early breathing difficulty experienced after acute high–dose
ozone inhalation, as these symptoms and particularly the result of inflammatory
precursors, is believed to probably only set in at a later stage.
Although the potential advantages of ozone in certain fields of medicine are not
disputed, ozone, depending on its concentration and cumulative dose, can be either therapeutic or toxic. Observations in this study emphasised that even short bursts of
high–dose ozone inhalation have deleterious effects on respiratory health and care
should be taken not to jump to conclusions regarding ozone’s medical application
without relevant scientific evidence. It must be stressed that high–dose inhalation of
ozone should be avoided at all cost – especially by those with existing airway
diseases. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2011.

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nwu/oai:dspace.nwu.ac.za:10394/4650
Date January 2010
CreatorsLotriet, Cornelius Jacob
PublisherNorth-West University
Source SetsSouth African National ETD Portal
Detected LanguageEnglish
TypeThesis

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