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Title
Oxidative stress, antioxidant defences and aging.
Author
Lenaz G; Cavazzoni M; Genova ML; DAurelio M; Pich MM; Pallotti
F; Formiggini G;
Marchetti M; Castelli GP; Bovina C
Source
Biofactors, 1998, 8:3-4, 195-204
Abstract
Apoptosis and aging share common mechanisms in oxidative stress
and mitochondrial
involvement. Treatment of cultured neuroblastoma cells with a
radical initiator induced
apoptosis; raise in hydrogen peroxide and release of cytochrome
c from mitochondria
preceded collapse of mitochondrial potential and cell death.
In rat hepatocytes treated with
adriamycin incubation with exogenous Coenzyme Q10 counteracted
the drug-induced
increase of hydrogen peroxide and the fall of the mitochondrial
potential, thus demonstrating
the quinone antioxidant effect. Complex I activity and its rotenone
sensitivity decreased in
brain cortex non-synaptic mitochondria from old rats; a 5 kb
mitochondrial DNA deletion
was found only in the old rats. A similar behavior was found
in human platelets from old
individuals. The postulated energy decline was confirmed by the
inhibitor sensitivities of
platelet aggregation and lactate production. The lack of the
5 kb deletion in platelets throws
doubts on mitochondrial DNA lesions as the only causes of mitochondrial
dysfunction in
aging.
Title
Coenzyme Q10 in vesicles composed of archaeal ether lipids or
conventional lipids
enhances the immuno-adjuvanticity to encapsulated protein.
Author
Makabi Panzu B; Sprott GD; Patel GB
Source
Vaccine, 1998 Oct, 16:16, 1504-10
Abstract
Cellular accumulation, tissue distribution, and immuno-adjuvanticity
were evaluated for
liposomal CoQ10 prepared from either
distearoylphosphatidylcholine:dicetylphosphate:cholesterol (4:1:5,
mol. ratio) (conventional
liposomes) or from the total polar lipids of the archaeon Methanosarcina
mazei
(archaeosomes). Liposomal CoQ10 vesicles of approximately 100
nm diameter, containing
up to 179 mumol of CoQ10 per mg of lipid have been evaluated
using J774A.1
macrophages and Balb/c mice. Archaeosomes uptake by J774A.1 macrophages
was better
than with the conventional liposome, and the incorporation of
CoQ10 enhanced the uptake
of both lipid vesicle types. All vesicle types were detected
in the liver and spleen of mice
(4-27% of injected dose) within 3 h of intraperitoneal injection.
Moreover, incorporation of
CoQ10 into lipid vesicles enhanced the immuno-adjuvanticity of
both conventional
liposomes and archaeosomes, to achieve approximately a doubling
in the titres of
BSA-specific antibody in sera to 169 and 430 micrograms ml-1,
respectively. Increases in
IgG1 and IgG2a/2b accounted for most of the CoQ10-induced increases
in anti-BSA titres.
These results are rationalized on the basis of surface hydrophobicity
and opsonization
changes induced by the presence of CoQ10 in vesicles. We suggest
that liposomal CoQ10
has potential as a new generation of vaccine delivery system
to enhance the immune
response. Its use as a novel delivery system may be particularly
effective under pathological
conditions where the occurrence of an oxidative stress condition
significantly impairs the
immune system functions.
Title
Mitochondria in neuromuscular disorders.
Author
DiMauro S; Bonilla E; Davidson M; Hirano M; Schon EA
Source
Biochim Biophys Acta, 1998 Aug, 1366:1-2, 199-210
Abstract
This review considers primary mitochondrial diseases affecting
the respiratory chain. As
diseases due to mitochondrial DNA defects defy traditional anatomical
classifications, we
have not limited our discussion to neuromuscular disorders, but
have extended it to include
mitochondrial encephalomyopathies. Primary mitochondrial diseases
can be due to
mutations in either the nuclear or the mitochondrial genome.
Nuclear mutations can affect (i)
genes encoding enzymatic or structural mitochondrial proteins;
(ii) translocases; (iii)
mitochondrial protein importation; and (iv) intergenomic signaling.
We review briefly recent
molecular data and outstanding questions regarding these mendelian
disorders, with special
emphasis on cytochrome c oxidase deficiency and coenzyme Q10
deficiency. Mitochondrial
DNA mutations fall into three main categories: (i) sporadic rearrangements
(deletions/duplications); (ii) maternally inherited rearrangements
(duplications); and (iii)
maternally inherited point mutations. We summarize the most common
clinical
presentations and discuss pathogenic mechanisms, which remain
largely elusive.
Uncertainties about pathogenesis extend to the process of cell
death, although excitotoxicity
in neurons and apoptosis in muscle seem to have important roles.
Title
The lipids of Pneumocystis carinii.
Author
Kaneshiro ES
Source
Clin Microbiol Rev, 1998 Jan, 11:1, 27-41
Abstract
Information about a number of Pneumocystis carinii lipids obtained
by the analyses of
organisms isolated and purified from infected lungs of corticosteroid-immunosuppressed
rats has been reported in recent years. Of the common opportunistic
protists associated with
AIDS (Cryptosporidium, Toxoplasma, and the microsporidia), more
is currently known
about the lipids of P. carinii than the others. Lipids that are
synthesized by the organism but
not by humans are attractive targets for drug development. Thus,
the elucidation of delta
7C-24-alykylated sterol and cis-9,10-epoxystearic acid biosyntheses
in P. carinii is currently
being examined in detail, since these have been identified as
P. carinii-specific lipids. The
development of low-toxicity drugs that prevent sterol C-24 alkylation
and the specific
inhibition of the lipoxygenase that forms cis-9,10-epoxystearic
acid might prove fruitful.
Although humans can synthesize coenzyme Q10, the anti-P. carinii
activity and low toxicity
of ubiquinone analogs such as atovaquone suggest that the electron
transport chain in the
pathogen may differ importantly from that in the host. Although
resistance to atovaquone
has been observed, development of other naphthoquinone drugs
would provide a broader
armamentarium of drugs to treat patients with P. carinii pneumonia.
Studies of
bronchoalveolar lavage fluid and of infected lungs have demonstrated
that the infection
causes a number of chemical abnormalities. Bronchoalveolar lavage
fluid obtained after the
removal of lung cellular material and the organisms has been
shown to contain larger
amounts of surfactant proteins and smaller amounts of phospholipids
than do comparable
samples from P. carinii-free lungs. Increased phospholipase activity,
inhibition of surfactant
secretion by type II cells, and uptake and catabolism of lipids
by the pathogen may explain
this phenomenon related to P. carinii pneumonia. Although not
yet thoroughly examined,
initial studies on the uptake and metabolism of lipids by P.
carinii suggest that the organism
relies heavily on exogenous lipid nutrients.
Title
Suppression of the formation of megamitochondria by scavengers
for free radicals.
Author
Wakabayashi T; Adachi K; Matsuhashi T; Wozniak M; Antosiewicz
J; Karbowsky M
Source
Mol Aspects Med, 1997, 18 Suppl:, S51-61
Abstract
In the present study we have attempted to suppress the formation
of megamitochondria by
scavengers for free radicals since conditions for the formation
of megamitochondria are
often intimately related to the generation of free radicals.
We employed three different
experimental conditions to induce megamitochondria in the liver:
ethanol, hydrazine and
chloramphenicol (CP). Scavengers for free radicals tested were:
alpha-tocopherol, coenzyme
Q10(CoQ10) and 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl(4-OH-TEMPO).
Allopurinol (AP), a xanthine oxidase inhibitor, was also tested.
Results obtained were as
follows. (1) Changes observed in the liver of animals treated
with ethanol, hydrazine or CP
were: formation of megamitochondria; decreases in the body weight
and the weight of the
liver; remarkable increases in the level of lipid peroxidation;
increases in the activity of
xanthine oxidase. (2) 4-OH-TEMPO was most effective in improving
these changes. A
mechanism of the formation of megamitochondria is proposed stressing
the role of free
radicals in the mechanism.
Title
Antioxidant ascorbate is stabilized by NADH-coenzyme Q10 reductase
in the plasma
membrane.
Author
Gómez Díaz C; Rodríguez Aguilera JC; Barroso
MP; Villalba JM; Navarro F; Crane FL;
Navas P
Source
J Bioenerg Biomembr, 1997 Jun, 29:3, 251-7
Abstract
Plasma membranes isolated from K562 cells contain an NADH-ascorbate
free radical
reductase activity and intact cells show the capacity to reduce
the rate of chemical oxidation
of ascorbate leading to its stabilization at the extracellular
space. Both activities are
stimulated by CoQ10 and inhibited by capsaicin and dicumarol.
A 34-kDa protein (p34)
isolated from pig liver plasma membrane, displaying NADH-CoQ10
reductase activity and
its internal sequence being identical to cytochrome b5 reductase,
increases the
NADH-ascorbate free radical reductase activity of K562 cells
plasma membranes. Also, the
incorporation of this protein into K562 cells by p34-reconstituted
liposomes also increased
the stabilization of ascorbate by these cells. TPA-induced differentiation
of K562 cells
increases ascorbate stabilization by whole cells and both NADH-ascorbate
free radical
reductase and CoQ10 content in isolated plasma membranes. We
show here the role of
CoQ10 and its NADH-dependent reductase in both plasma membrane
NADH-ascorbate
free radical reductase and ascorbate stabilization by K562 cells.
These data support the idea
that besides intracellular cytochrome b5-dependent ascorbate
regeneration, the extracellular
stabilization of ascorbate is mediated by CoQ10 and its NADH-dependent
reductase.
Title
Recent nutritional approaches to the prevention and therapy of
cardiovascular disease.
Author
Kendler BS
Source
Prog Cardiovasc Nurs, 1997 Sum, 12:3, 3-23
Abstract
Nutritional factors play an important role in the development
and treatment of cardiovascular
disease (CVD). However, health care professionals may overlook,
or even disregard, some
of these factors for several reasons, including inadequate training
and conflicting reports in
the biomedical literature. This review provides a synopsis of
more than two-dozen
nutritional approaches to primary and secondary prevention and
therapy of CVD. Favorable
cardiovascular effects have been reported with the use of unsaturated
fatty acids, vegetarian
and semi-vegetarian diets, dietary fiber, plant sterols, alcoholic
beverages, vitamins (niacin,
E, C, B6, B12, folate), minerals (potassium, calcium, magnesium,
selenium),
conditionally-essential nutrients (coenzyme Q10, L-carnitine,
taurine) and botanical agents
(garlic, hawthorn, gugulipid). In contrast, trans-fatty acids,
oxysterols, homocysteinemia,
carbohydrate intolerance, and excessive sodium chloride and iron
have been associated with
undesirable cardiovascular effects. A nutritional approach to
CVD provides a pivotal
adjuvant to traditional pharmaceutical and/or surgical interventions
by maximizing the
likelihood of success in decreasing CVD morbidity and mortality
and minimizing the
economic and social costs associated with this disease.
Title
Coenzyme Q10 treatment in mitochondrial encephalomyopathies.
Short-term double-blind,
crossover study.
Author
Chen RS; Huang CC; Chu NS
Source
Eur Neurol, 1997, 37:4, 212-8
Abstract
We report a short-term double-blind, crossover study of CoQ10
in 8 patients with
mitochondrial encephalomyopathies. Four patients had myoclonus
epilepsy with ragged-red
fibers syndrome, 3 had mitochondrial myopathy, encephalopathy,
lactic acidosis and
stroke-like episodes syndrome, and 1 had chronic progressive
external ophthalmoplegia
with myopathy. A trend of effectiveness of CoQ10 in several parameters
was noted.
Fatigability of daily activities was alleviated. The endurance
to muscle exercise was
augmented. Global muscle strength scored by Medical Research
Council scale was
increased. The extent of elevation in serum lactate and pyruvate
levels after exercise was
decreased. However, only the global MRC index score had a statistical
significance (p <
0.05). There were no side effects during therapy. The serum CoQ10
levels were
significantly lower in patients than in normal controls before
CoQ10 treatment and increased
significantly after treatment.
Title
Natural products and their derivatives as cancer chemopreventive
agents.
Author
Ren S; Lien EJ
Source
Prog Drug Res, 1997, 48:, 147-71
Abstract
This review summarizes currently available data on the chemopreventive
efficacies,
proposed mechanisms of action and relationships between activities
and structures of natural
products like vitamin D, calcium, dehydroepidandrosterone, coenzyme
Q10, celery seed oil,
parsley leaf oil, sulforaphane, isoflavonoids, lignans, protease
inhibitors, tea polyphenols,
curcumin, and polysaccharides from Acanthopanax genus.
Title
Exogenous reactive oxygen species deplete the isolated rat heart
of antioxidants.
Author
Vaage J; Antonelli M; Bufi M; Irtun O; DeBlasi RA; Corbucci GG;
Gasparetto A; Semb
AG
Source
Free Radic Biol Med, 1997, 22:1-2, 85-92
Abstract
The effects of reactive oxygen species (ROS) on myocardial antioxidants
and on the activity
of oxidative mitochondrial enzymes were investigated in the following
groups of isolated,
perfused rat hearts. I: After stabilization the hearts freeze
clamped in liquid nitrogen (n = 7).
II: Hearts frozen after stabilization and perfusion for 10 min
with xanthine oxidase (XO) (25
U/l) and hypoxanthine (HX) (1 mM) as a ROS-producing system (n
= 7). III: Like group
II, but recovered for 30 min after perfusion with XO + HX (n
= 9). IV: The hearts were
perfused and freeze-clamped as in group III, but without XO +
HX (n = 7). XO + HX
reduced left ventricular developed pressure and coronary flow
to approximately 50% of the
baseline value. Myocardial content of hydrogen peroxide (H2O2)
and malondialdehyde
(MDA) increased at the end of XO + HX perfusion, indicating that
generation of ROS and
lipid peroxidation occurred. Levels of H2O2 and MDA normalized
during recovery.
Superoxide dismutase, reduced glutathione and alpha-tocopherol
were all reduced after
ROS-induced injury. ROS did not significantly influence the tissue
content of coenzyme
Q10 (neither total, oxidized, nor reduced), cytochrome c oxidase,
and succinate cytochrome
c reductase. The present findings indicate that the reduced contractile
function was not
correlated to reduced activity of the mitochondrial electron
transport chain. ROS depleted the
myocardium of antioxidants, leaving the heart more sensitive
to the action of oxidative
injury. |
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