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Lipid peroxidation
increases in a variety of tissues with advancing
age (Yu, 1993). Lipid peroxidation is a well-established
mechanism of cellular injury, leading to the
destruction of membrane lipids and the production
of lipid peroxides and their by-products, such
as aldehydes. Malonaldehyde (MDA) and 4-hydroxyalkenals,
such as 4-HNE, are end products derived from
the breakdown of polyunsaturated fatty acids
and related esters. Measurement of such aldehydes
provides a convenient index of lipid peroxidation
(Esterbauer and Cheeseman, 1990).
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2005
Departments of
Dermatology, Faculty of Medicine, Zonguldak
Karaelmas University, Zonguldak, Turkey.
Background: The pathophysiology of alopecia
areata (AA) has not been clearly defined;
however, it appears as a tissue-restricted
autoimmune disease mediated by T lymphocytes.
Immunohistochemical studies have shown
peri- and infra-follicular inflammatory
infiltrate which damages hair follicles.
We analyzed the role of lipid peroxidation
and oxidant-antioxidant enzymes in the
pathogenesis of AA. Material/Methods:
Twenty-four patients with AA and 20
age- and sex-matched healthy controls
were enrolled in this study. We analyzed
serum levels of malondialdehyde (MDA)
and nitric oxide (NO) and the serum
activities of superoxide dismutase (SOD)
and xanthine oxidase (XO) in patients
with AA and control subjects. Results:
The levels of MDA and NO (nitrite/nitrate)
and the activity of XO in serum of patients
with AA (0.76+/-0.34 nmol/ml, 14.88+/-6.40
nmol/ml, and 0.34+/-0.10 U/ml, respectively)
were significantly higher than those
of controls (0.35+/-0.09 nmol/ml, 10.71+/-1.75
nmol/ml, 0.11+/-0.03 U/ml; p<0.001,
p<0.001, p<0.05, respectively).
The SOD activity (12.95+/-2.16 U/ml)
in the serum of patients with AA was
significantly lower than that of controls
(14.89+/-2.29 U/ml, p<0.05). Conclusions:
Increased lipid peroxidation in AA may
be related to an increase in NO level
and XO activity and a decrease in SOD
activity. These results suggest that
lipid peroxidation and alterations in
the oxidant-antioxidant enzymatic system
may play a role in the pathogenesis
of AA.
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Division of Drug
Target Discovery and Development, Central
Drug Research Institute, Chatter Manzil
Palace, Mahatma Gandhi Marg, Lucknow 226001,
Uttar Pradesh, India.
Severe hemolysis or
myolysis occurring during pathological
states, such as sickle cell disease,
ischemia reperfusion, and malaria results
in high levels of free heme, causing
undesirable toxicity leading to organ,
tissue, and cellular injury. Free heme
catalyzes the oxidation, covalent cross-linking
and aggregate formation of protein and
its degradation to small peptides. It
also catalyzes the formation of cytotoxic
lipid peroxide via lipid peroxidation
and damages DNA through oxidative stress.
Heme being a lipophilic molecule intercalates
in the membrane and impairs lipid bilayers
and organelles, such as mitochondria
and nuclei, and destabilizes the cytoskeleton.
Heme is a potent hemolytic agent and
alters the conformation of cytoskeletal
protein in red cells. Free heme causes
endothelial cell injury, leading to
vascular inflammatory disorders and
stimulates the expression of intracellular
adhesion molecules. Heme acts as a pro-inflammatory
molecule and heme-induced inflammation
is involved in the pathology of diverse
conditions; such as renal failure, arteriosclerosis,
and complications after artificial blood
transfusion, peritoneal endometriosis,
and heart transplant failure. Heme offers
severe toxic effects to kidney, liver,
central nervous system and cardiac tissue.
Although heme oxygenase is primarily
responsible to detoxify free heme but
other extra heme oxygenase systems also
play a significant role to detoxify
heme. A brief account of free heme toxicity
and its detoxification systems along
with mechanistic details are presented.
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2002
Departments of
Genetics and Medical Genetics, University
of Wisconsin, 445 Henry Mall, Madison,
WI 53706, USA.
To examine molecular events associated
with brain aging and its retardation
by caloric restriction (CR), we have
employed high-density oligonucleotide
arrays providing data on 6347 genes
to define transcriptional patterns in
two brain regions (cerebellum and neocortex).
Male C57BL/6 mice were either fed normally
or subjected to CR. To investigate aging,
5 month (young adult) and 30 month-old
normally fed mice were compared. To
study CR, 30 month-old control and CR
mice were compared. In both brain regions,
aging resulted in a gene expression
profile suggestive of a marked inflammatory
response, oxidative stress and reduced
neuronal plasticity and neurotrophic
support. In the brain, CR selectively
attenuated the age-associated induction
of genes encoding inflammatory and stress
responses. In addition to providing
an improved understanding of the aging
process, the use of DNA microarrays
generates panels of hundreds of transcriptional
biomarkers of molecular aging, providing
a new tool to measure biological age
on a tissue-specific basis. These studies
suggest that genomic approaches may
be useful in understanding the molecular
basis of the aging process in experimental
animals.
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2000
Gerontology
Research Center, NIA/NIH, Baltimore,
MD 21224, USA.
Aging is accompanied by a decline
of functions controlled by the central
dopaminergic system, such as reduced
locomotor activity, motivation, impairment
of memory formation, and learning deficits.
The molecular mechanisms underlying
age-related impairment of dopaminergic
functions are unknown. Current literature
and our own recent work, which are reviewed
and summarized in the present paper,
suggest that dopamine oxidative stress
and its subsequent signaling may contribute
to the aging of dopaminergic system.
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