DHEA Protects Mice From Endotoxin Toxicity

[j.]

Another good reason to have good thyroid function and therefore good DHEA levels.

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production.

Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEA) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF). Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharide (LPS; 800 micrograms per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF-induced phenomena.

Link

 

[j.]

I'm not sure if I'm reading this correctly, but apparently cholesterol protects against endotoxin.

Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice

Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection.

Link

Another paper:

The endotoxin-lipoprotein hypothesis – an update

Hypercholesterolaemia is a well-defined risk factor for both morbidity and
mortality in coronary artery disease. However, in chronic heart failure high levels
of plasma cholesterol have been associated with better survival. The reason for
this inverse epidemiology is potentially explained by the ability of plasma
lipoproteins to bind and detoxify bacterial lipopolysaccharide (LPS, endotoxin),
a cell-wall component of Gram-negative bacteria. This hypothesis has been
termed the “endotoxin-lipoprotein hypothesis”, first published in 2000. LPS is
one of the strongest inducers of pro-inflammatory cytokine release in heart
failure. This article summarises the known pathophysiology of increased
endotoxin concentrations entering the blood stream via the hypoperfused
oedematous bowel wall. Furthermore, it discusses technical problems with the
measurement of LPS, and reviews its signalling cascade and the biological effects
of LPS as well as the potentially protective ability of serum lipoproteins in chronic
heart failure.

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Endotoxemia is associated with rapid and marked declines in serum levels of LDL and HDL by unknown mechanisms.

 

[Suikerbuik]

I'm not sure if I'm reading this correctly.

Yes you do, not sure if this is the only mechanism but one is that chylomicrons and lipoproteins 'contain' lipopolysaccharide binding proteins (LBPs).

Just a random study: http://www.ncbi.nlm.nih.gov/pubmed/11160139. I think if you try search more specific you will fiond more interesting information. Probably this is why cholesterol is found to be one of the most protective substances that 'prevent' heart disease and more.

Edit: 'preventive' in a manner that the mortality rates of heart dissease are significantly lower as with other diseases when having moderate cholesterol compared to low.

 

[Such_Saturation]

Ray Peat has said cholesterol protects from endotoxin (90% sure).

 

[j.]

Apparently pregnenolone is protective in some situations.

Effect of Exogenous Steroids and Inhibitors of Steroidogenesis on Endotoxin Shock

Suppression of corticosteroid production by inhibitors effected a tenfold increase in susceptibility of mice to death from endotoxin shock. Amphenone B and metyrapone caused some increase in susceptibility, but if given more than 1 hr before the endotoxin afforded protection to the test animals. Aminoglutethimide exerted a deleterious effect for at least 24 hr. The effect of the aminoglutethimide was reversed by pregnenolone, progesterone and deoxycorticosterone, although the LD50 remained lower than in the control animals. Corticosterone, cortisone and hydrocortisone afforded marked protection in both the endotoxin treated mice as well as the endotoxin-inhibitor treated mice. Andros-tenedione caused a decrease in the LD50 value in both the control and aminoglutethimidetreated mice. By contrast 17-a-hydroxyprogesterone afforded no protection against endotoxin in the control mice and a significant, but miniscule, degree of protection in the inhibitor-treated mice.

 

[milk_lover]

Great find! I think when I supplement DHEA with starch, I hardly get any endotoxin symptoms. @haidut would you classify DHEA with vitamin A, vitamin D, and B2 as good protection from endotoxins? I read also on the site that glycine is good for endotoxin protection.

 

[haidut]

Great find! I think when I supplement DHEA with starch, I hardly get any endotoxin symptoms. @haidut would you classify DHEA with vitamin A, vitamin D, and B2 as good protection from endotoxins? I read also on the site that glycine is good for endotoxin protection.

I think vitamin D and emodin are the most direct endotoxin antagonist as they block the receptor through which it works. Other substances like niacinamide, glycine, etc are also good but they block most of the actual endotoxin effects and not the entire cascade like a receptor antagonist would do. So, they have different effects and as such using them in cobination is probably going to be even more effective.