Antaeus Labs: AEGIS

There are many types of liver injury, but only one is normally associated
with the use of oral androgens -- cholestasis. This condition is defined as
a failure of normal bile to reach the duodenum, which may be due to a
number of different pathological states between the hepatocyte and the
ampulla of Vater. When one takes oral androgens (typically methylated at
C17a) the physical structure of the hepatocyte is altered -- microfilaments
and canaliculi become less contractile. Disruptions in the canalicular bile
salt export pump may also occur. This leads to impaired bile flow and the
retention of highly cytotoxic hydrophobic bile salts. At low
concentrations, these retained bile salts cause apoptosis; at higher
concentrations, necrosis and severe liver damage.

This is where AEGIS comes into the picture. It was designed with users of
oral androgens in mind, and brings together the best anti-cholestatic
ingredients available.

Tauroursodeoxycholic acid:

-Can prevent apoptosis during cholestasis. Toxic bile acids produce
apoptosis Via fas- and TRAIL- death receptor mediated pathways. Both are,
to some degree, dependent on the translocation of the 'bax' pro-apoptoic
molecule from the cytosol of hepatocytes to the cell mitochondria. TUDCA
prevents bax translocation, strongly stabilizes mitochondrial membranes,
and activates the MAPK pro-survival pathway in hepatocytes.
(ref<http://www.jlr.org/content/50/9/1721.full.pdf>)
These effects protect hepatocytes from bax-related apoptosis.

-Is a hydrophilic bile acid, and its presence markedly shifts the bile pool
towards hydrophilicity, which, to some extent, detoxifies it. When used
consistently, especially at pharmacological doses, TUDCA (along with UDCA)
eventually becomes the predominant bile acid in the liver and in general
circulation. (ref<http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.1999.00596.x/pdf>
)

-Directly stimulates bile secretion via modulating cellular signalling
pathways in hepatocytes, such as ERK, src, PKC and others. These signalling
pathways generally phosphorylate, or activate, the bile salt export pump
(BSEP) and other processes involved in bile export/secretion. (For example,
PKC-alpha-mediated secretion of HCO3-.)
(ref<http://www.ncbi.nlm.nih.gov/pubmed/12730886?dopt=Abstract&holding=npg>
, ref<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589332/pdf/yjbm00029-0062.pdf>
, ref <http://www.nature.com/labinvest/journal/v86/n2/full/3700371a.html>)

Polyenylphosphatidylcholine:
-Stabilizes cellular membranes and dilates bile canaliculi. This former
effect has been shown to protect human cells from hydrophobic bile salt
induced apoptosis
(ref<http://www.ncbi.nlm.nih.gov/pubmed/12730886?dopt=Abstract&holding=npg>
), and the latter may serve to counteract the reduction in contractility
seen in androgen-induced cholestasis.
(ref<http://www.ncbi.nlm.nih.gov/pubmed/706511>
)

-Oral androgen administration may decrease hepatic Na+, K+-ATPase, Ca2+, Mg
2+-ATPase and F-actin levels --- all of which may be restored, and even
raised, by polyenylphosphatidylcholine administration.
(ref<http://www.sciencedirect.com/science/article/pii/S0024320503002923>
)
-Is secreted into bile by hepatocytes, where it serves as a major component
of the micelles in which bile acids are emulsified. Increased levels of
biliary phosphatidylcholine reduces the cytotoxicity of bile acids, whereas
phosphatidylcholine-secretion impairment (as is often seen in ABCB4
disease) is characterized by extremely severe cholestatic liver disease. (
ref <http://www.ncbi.nlm.nih.gov/pubmed/19273348>)

To summarize: Aegis is highly-potent, highly-specific liver protection for
people taking hepatotoxic oral androgens. Superior protection cannot be
bought, nor should it be needed.

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