The Association of Oxidative Stress and Nasal Polyposis
E EKIN
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OM IPCIOGLU
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BE ERKUL
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B KAPUCU
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O OZCAN
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H CINCIK
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A GUNGOR
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Dr Engin ekin GATA, Haydarpasa Egitim Hastanesi, KBB Klinigi, 34668 Kadky, Istanbul,
Turkey
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The Journal of International Medical Research
2009; 37: 325 330 [first published online as 37(2) 2]
The Association of Oxidative Stress and
Nasal Polyposis
1Department of Otolaryngology, and 2Department of Biochemistry, Gulhane Military
Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey
Many diseases are linked to damage from
reactive oxygen species that occurs from
an imbalance between reactive oxygen
species and antioxidants, a condition
called oxidative stress. Nasal polyposis is
considered to be an inflammatory
condition in nasal and paranasal sinus
cavities and its aetiology is still unclear.
There are very few data on epithelial
changes in nasal polyposis and their
relationship with free radical damage.
Malondialdehyde as a major end-product
of lipid peroxidation, and superoxide
dismutase and nitric oxide as
antioxidants play important roles in
oxidative stress. In this study, the
concentrations of malondialdehyde,
superoxide dismutase and nitric oxide
were compared in normal and nasal
polyposis-affected tissue samples.
Malondialdehyde levels were significantly
higher, and superoxide dismutase and
nitric oxide levels were significantly lower
in patients with nasal polyposis compared
with the control group. This study
demonstrates that there is a strong
relationship between oxidative stress and
the pathogenesis of nasal polyposis.
Introduction
Nasal polyposis is considered an
inflammatory condition in nasal and
paranasal sinus cavities and is often
encountered in otolaryngology clinics.
Despite the prevalence and recognition of
this condition for 3000 years, its aetiology
has remained unclear. There have been
many suggestions about the aetiology of
nasal polyposis, including adenoma,
fibroma, glandular cyst, mucosal exudates,
blockade, glandular hyperplasia, new gland
formation, ion transport, periphlebitis,
perilymphangitis, cystic dilatation of the
excretory duct, vessel obstruction and
necrotizing ethmoiditis; however multiple
factors may be involved in polyp formation
and the precise aetiology of nasal polyposis
is still unknown.1,2 Most studies in the
literature deal with the inflammatory
mechanisms occurring in the lamina propria
of nasal polyposis, but few data are
available on epithelial changes and their
relationship with free radical damage.3
The nasal epithelium represents the
respiratory systems first line of defence
against inhaled stimuli, such as chemical
pollutants and allergens, and is thought to
have an important role in the regulation of
nasal inflammatory disease through the
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release of cytokines, platelet-activating
factor and prostanoids, and the expression of
adhesion molecules. Resultant free radical
damage to lipids (peroxidation), proteins
and DNA leads to various forms of cell
injury.4 An important mechanism in the
development of cell injury due to reactive
oxygen species is lipid peroxidation of
polyunsaturated fatty acids in cell
membranes, which forms products such as
malondialdehyde, an end-product of lipid
peroxidation.
Many diseases are linked to damage from
reactive oxygen species that occurs from an
imbalance between reactive oxygen species
and scavenging systems (antioxidants), i.e.
oxidant/antioxidant imbalance, a condition
known as oxidative stress. Superoxide
dismutase that catalyses the dismutation of
superoxide anions is the first and the most
important line of antioxidant enzyme
defence against reactive oxygen species. The
isozymes of the superoxide dismutase family
are crucial for modulation of the activity of
nitric oxide, a gaseous free radical believed
to play a role in the physiology and
pathology of the respiratory tract and an
important regulator of several biological
functions. Nitric oxide is known to be
produced from various types of cells and
tissues in response to inflammatory
stimulation and to be an important
regulator of immune surveillance, including
antiviral and bactericidal effects; however,
nitric oxide also inhibits cell proliferation,
DNA synthesis and collagen production.5 9
Previous studies have reported decreased
nasal nitric oxide levels in patients with
chronic rhinosinusitis and nasal polyposis in
general, and also in patients with cystic
fibrosis, even before the onset of chronic
respiratory tract infections.10,11
Nitric oxide is generated from arginine by
a family of enzymes known as the nitric
oxide synthases, and acts as an autocrine
and paracrine messenger. It also has an
important role in non-specific host defence
because of its cytotoxicity toward tumour
cells and micro-organisms. Since nitric oxide
and oxygen both contain an unpaired
electron, they rapidly react together, leading
to their reciprocal inactivation and
eventually the formation of peroxynitrite
which, in turn, induces protein tyrosine
nitration, although other mechanisms such
as oxidation of nitrites by myeloperoxidase
can also induce similar protein alterations.12
Ruffoli et al.13 suggested that progressive
epithelium injury in polyp tissues is caused
by peroxynitrite. In addition to the toxic
effect, this reaction might reduce the
concentration of nitric oxide, thereby
decreasing its bioavailability.14 The aim of
this study was to investigate the role of
malondialdehyde, superoxide dismutase and
nitric oxide in nasal polyposis by comparing
their concentrations in samples from nasal
polyposis-affected and normal tissues.
Patients and methods
PATIENTS AND STUDY DESIGN
This prospective, randomized, controlled
study was designed and conducted from
February 2007 to May 2008 at the
Otolaryngology Head and Neck Surgery
Department and the Biochemistry
Department of Gulhane Military Medical
Academy, Haydarpasa Training Hospital,
Istanbul, Turkey. The study was approved by
the Research Scientific Committee of
Gulhane Military Medical Academy and
informed written consent was obtained from
all study participants.
Male and female subjects were allocated
into two groups, those with nasal polyposis
(study group) and those without nasal
polyposis who were healthy except for nasal
septal deviation (control group). The
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diagnosis of nasal polyposis was based on
anterior rhinoscopy, endoscopic endonasal
examination and paranasal sinus
computerized tomography scanning.
Patients who had a history of nasal allergy,
asthma, previous nasal surgery, acute
infection, systemic disease, or aspirin
sensitivity were excluded from either of the
two groups. Nasal polyp tissue specimens
were obtained from patients with nasal
polyposis when they underwent endoscopic
sinus surgery and were all reported as
inflammatory polyps by the Pathology
Department of Haydarpasa Train (...truncated)