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Science Forum Index » Life Extension Forum » STATINS REDUCE GLUTATHIONE LEVELS AND INCREASE...
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| maudereagan |
 Posted: Sun May 04, 2008 7:31 am |
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Joined: 30 Apr 2005
Posts: 108
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Glutathione is a major antioxidant within the body and brain and
caspace 3 activation results in apoptosis---cell death which is
beneficial for malignant tumors but in other cells, not so much unless
they are ubiquinated (selected for disposal).....http://
www.toxicology.org/AI/FA/2005_Toxicologist.pdf
SOT, 2005
ANTI-HYPERCHOLESTEROLEMIA DRUGS IN THE
STATIN CLASS REDUCE GLUTATHIONE LEVELS AND
INCREASE CASPASE 3 ACTIVATION IN AN IN VITRO
CELL MODEL.
J. F. Pregenzer, J. M. McKim, Jr., P. C. Wilga and D. K. Petrella.
CeeTox,
Kalamazoo, MI.
The ability to identify and understand the potential adverse effects
of new drugs
early in the development process can help manage patient risk versus
clinical benefit.
Cerivastatin (CRV), simvastatin (SMV), lovastatin (LOV), atorvastatin
(ATV),
fluvastatin (FLV) and pravastatin (PRV) are in the statin class of
cholesterol lowering
drugs used in the treatment of hypercholesterolemia. All have been
associated
with hepatotoxicity and the skeletal muscle disorder rhabdomyolysis.
CRV was recently
withdrawn from United States markets because of reports of fatal
rhabdomyolysis
and high incidence of liver toxicity. It is believed that the
mechanisms underlying
these adverse effects are linked to energy depletion and apoptosis.
The
purpose of the present study was to screen the statin drugs in a
battery of in vitro assays
designed to evaluate cytotoxic, apoptotic, and oxidative stress
potential. Rat
hepatoma (H4IIE) cells were seeded into 96-well plates (10, 000/well).
Following a
48 hr equilibration period the cells were treated with compounds at
concentrations
of 0, 0.1, 1, 5, 10, 50, 100, and 300 uM for 24 hr. Cytotoxicity was
evaluated by
measuring membrane leakage, mitochondrial function, and cell number.
Oxidative
stress was assessed by measuring total glutathione (GSH) and 8-
isoprostane.
Apoptosis was determined via caspase 3 activity. The hydrophobic
statins (FLV,
CRV, SMV, LOV, and ATV) produced a modest decrease in ATP, cell
number, and
mitochondrial function, but had pronounced effects on the reduction of
total GSH
pools and induction of caspase 3 activity. In contrast, the
hydrophilic statin (PRV)
had no measurable effects in this system. These data are consistent
with published
studies in which the mechanism(s) associated with statin toxicity are
energy depletion
and induction of apoptosis. Moreover, these data indicate that early
screening
with a cell-based system that evaluates several biochemical processes
can provide
important information on the relative safety of new drugs prior to
entering animal
studies or beginning clinical trials. |
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| nightlight... |
| Posted: Sun May 04, 2008 7:50 am |
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Guest
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What a sweet deal for the Big Pharma. First they sell you expensive
statins, then for the rest of your life sell you drugs to treat all
the oxidative damage from diminished glutathione (along with all other
toxic side-effects of statins).
It's like government creating a drug war by criminalizing drug use
(which is as therapeutic for the social organism as statins are for
your organism), then making you pay in dollars and freedoms to fight
the problem of their own creation. |
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