ACTA BIOLOGICA CRACOVIENSIA

NUTRITIONAL CAROTENOIDS AND THEIR IMPLICATION IN HUMAN HEALTH
INVITED LECTURES
Carotenoid and retinoid metabolism in hepatic
stellate cells (HSCs) and their relationship to
hepatic disease
William S. Blaner1 , Igor Shmarakov1,2 1 Department of Medicine, Columbia University, New York, NY
10032, wsb2@columbia.edu
2 Department of Biochemistry, Chernivtsy National University,
Chernivtsy, Ukraine, igor.shmarakov@gmail.com
Approximately 70% of the retinoid (vitamin A and its metabolites)
present within most healthy mammals is found in the liver.
Within the liver, approximately 70-90% of retinoid is stored as
retinyl ester within lipid droplets that are a distinguishing characteristic
of hepatic stellate cells (HSCs). The HSC lipid droplets
are also a site of hepatic β-carotene accumulation. HSCs possess
all of the metabolic machinery needed for metabolizing retinoids
and also express both carotene-cleaving enzymes, Bcmo1 and
Bcmo2. We have been interested in a number major questions
regarding HSC retinoid storage and metabolism. The first concerns
why evolution has selected the HSC as the site where the
majority of retinoid within the body is stored. We hypothesize the
retinoid storage within HSCs may protect the liver against injury.
To assess this possibility, we have employed four models to
induce liver injury, alcohol-induced liver disease, partial hepatectomy,
carcinogen induced hepatocellular carcinoma, and CCl4induced
hepatic fibrosis in wild type mice that can store and
mobilize retinoids normally, in LRAT-deficient mice which are
unable to store retinoid within the liver and in RBP-deficient mice
that store retinoid normally but which are unable to mobilize
hepatic retinoid stores. Outcomes from these studies suggest that
HSC retinoid storage and mobilization and carotenoid accumulation
may be important for preventing development of liver injury.
A second area of interest centers on the biochemical and cellular
processes involved in the genesis and dissolution of lipid droplets
present within hepatic stellate cells. Here, we are interested in
understanding processes important for the formation and
enlargement of these lipid droplets in times of excessive dietary
vitamin A intake and in the dissolution of these droplets in times
of diminished dietary vitamin A intake or upon injury to the liver.
Data from these lipid droplet studies will also be presented.
Effects of carotenoids on DNA damage and
repair: relevance to human disease
Andrew R. Collins
Department of Nutrition, University of Oslo, PB 1046 Blindern,
0316 Oslo, Norway, a.r.collins@medisin.uio.no
Carotenoids have been considered as likely candidates for a role
in protecting against disease for at least 20 years, and there is a
widespread belief that antioxidants in the diet, including
carotenoids, can prevent diseases such as cancer, cardiovascular
disease and diabetes by counteracting the oxidative damage to
biomolecules that is thought to underlie, or exacerbate, these diseases.
Carotenoids are classical radical scavengers, and their
ability to suppress oxidation in vitro has been demonstrated; for
instance, they prevent the oxidation of low density lipoprotein
particles by a free radical generating system. In cell culture, certain
carotenoids have been shown to decrease the oxidation of
DNA by H 2 O 2 .
To assess the relevance of these findings to human health, a
common approach is to use DNA oxidation in lymphocytes (measured
with the comet assay, single cell gel electrophoresis) as a
Vol. 53, suppl. 1, 2011
biomarker for the effectiveness of various antioxidants and
antioxidant-rich foods in vivo. An early finding was a negative correlation
between plasma carotenoid concentration and DNA base
oxidation in humans (though causality could not be deduced;
carotenoids might simply have acted as a marker of total fruit
and vegetable consumption, with another ingredient of those
foods being responsible for the effect). Intervention studies with
carotenoids as supplements have shown, in many but not all
cases, a decrease in endogenous DNA oxidation in lymphocytes
and an enhanced resistance to damage by H 2 O 2 ex vivo.
However good biomarkers are, they are not a substitute fror the
true endpoint, disease or death. Numerous clinical trials with βcarotene
supplementation have been carried out. A recent metaanalysis
(Bjelakovic et al., 2007) showed that β-carotene, vitamin A
and vitamin E, taken singly or together, actually increase mortality.
Whatever the role of carotenoids in vivo, it is unlikely that
antioxidant activity is the whole story. There is recent evidence
from cell culture experiments that β-cryptoxanthin enhances the
ability of cells to repair oxidation damage to bases in DNA (their
second line of defence), and this is supported by findings of
enhanced DNA base excision repair in humans given kiwifruit as
a supplement, or a diet rich in fruit and vegetable products. But
we are still far from understanding how the complex mix of phytochemicals
in fruits and vegetables protects us from disease.
REFERENCE:
BJELAKOVIC et al. 2007. JAMA 297: 842-857.
17–22 July 2011, Krakow, Poland
Lutein and zeaxanthin: relationships to
cognitive function in the elderly
Elizabeth J. Johnson
Carotenoids & Health Laboratory, Tufts University, Boston, MA,
USA
Cognitive impairment affects nearly one in four communitydwelling
elders and is a major risk factor for development of
dementia later in life. Cognitive impairment in the elderly is
receiving increased attention because of the possibility that early
intervention may prevent or delay progression to dementia.
Findings from our studies suggest that the xanthophylls, lutein
(L) and zeaxanthin (Z), which benefit individuals with early stage
age-related macular degeneration, may also be important in cognitive
function in the elderly. L and Z cross the blood brain barrier
and exclusively accumulate in the macular region of the retina,
where they are referred to as macular pigment (MP). In a
study of healthy older adults, MP was found to be significantly
related to cognitive tests that assessed processing speed, accuracy
and completion ability. Our work in primates showed that retinal
L and Z were significantly related to brain L and Z concentrations.
MP is thus a biomarker for brain L and Z concentrations.
In the Georgia Centenarian Study population we found that
among the serum carotenoids, L had the strongest relationships
with global cognitive function, memory, recall, retention, verbal
fluency, and dementia severity. In decedents of the same study we
found that brain Z concentration was significantly related to antemortem
measures of global cognitive function, memory, verbal
fluency and dementia severity after adjusting for age, education,
sex and self-reported diabetes or hypertension. Brain L concentration
was related to recall and verbal fluency, but the associations
were attenuated after adjustment for covariates. We have
also shown that L supplementation significantly improved verbal
fluency scores in healthy older women. The sum of our findings
suggests that L and Z embedded in brain tissue are capable of
influencing cognitive function in the elderly. Additional research
will be necessary to confirm these relations.
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