Endotoxin Antagonists - Part IV
 
Endotoxin Antagonists - Part IV

Part 1 https://www.patreon.com/posts/6962156 

Part 2 https://www.patreon.com/posts/endotoxin-part-7130268 

Part 3 https://www.patreon.com/posts/endotoxin-part-7139683 

Some terms:

Endotoxin - Product of some bacteria structure known to cause inflammation. Also known as lipopolysaccharide and abbreviated to LPS. Part of gram negative bacteria cell wall.

CD14 - A protein involved detection of endotoxin.

TLR4 - A protein involved detection of endotoxin.

TLR2 - A protein involved detection of endotoxin.

MyD88 - A protein involved detection of endotoxin.

NFKB - Protein involved in genetic transcription changes in response to stress.

LBP    - Lipopolysaccharide binding protein. Binds endotoxin after detection.


The sequence of detection to inflammation is (partially)

LPS->LBP>CD14>TLR4>NFKB>TNFa >IL-(x)>COX(x)


TNF/TNFa > Inflammatory cytokine

IL-1b > Inflammatory cytokine linked to pain

IL-6 > An inflammatory cytokine and an anti-inflammatory myokine.

Il-8 > Inflammatory cytokine


iNOS > An enzyme catalysing the production of nitric oxide, induced by cytokines.

COX > Cyclooxygenase, a family of enzymes involved in the formation of prostaglandins.

Glycine

Production of superoxide and TNF-alpha from alveolar macrophages is blunted by glycine. 

Inflammation from endotoxin can cause  lung problems either from inhalation or peripheral circulation. In cell models glycine can blunt increases in TNF-Alpha, superoxide,  and intracellular calcium. 


Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. 

In rodent models dietary glycine lowers mortality from endotoxin and lowers tumour necrosis factor alpha. Glycine protects the lungs but not the liver from the damage due to endotoxin.


Amino acids and asthma: a case-control study. 

Endotoxin is thought to be causal in some types of asthma, in one analysis of serum amino acids glycine was strongly associated with lower risk for asthma.

Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle. 


Glutamine

Glutamine decreases inflammation in infant rat endotoxemia 

In rodents injected with endotoxin, concurrent glutamine administration minimises the decrease in plasma glutamine and reduces the concentration of both proinflammatory and anti-inflammatory cytokines.


Glutamine induces heat shock protein and protects against endotoxin shock in the rat

Glutamine increases heat shock protein and dramatically reduces mortality while protecting organs from endotoxin damage.


Glutamine attenuates endotoxin-induced lung metabolic dysfunction: Potential role of enhanced heat shock protein 70 

Glutamine attenuates lung damage from endotoxin.


Glutamine attenuates tumor necrosis factor-α release and enhances heat shock protein 72 in human peripheral blood mononuclear cells TNFA Antagonist 

Glutamine decreases TNFa, while increasing heat shock protein 72 in peripheral blood polymorphonuclear cells.


*Glutamine may not be suitable for frequent supplementation to lower low grade endotoxemia and inflammation,  it’s perhaps best seen as an emergency treatment for sepsis.*


Zinc

Polaprezinc Protects Mice against Endotoxin Shock 

Zinc carnosine decreased mortality, plasma nitric oxide and TNFa after endotoxin administration. It also mitigated related lung damage and increase in nitric oxide. It’s thought to work by zinc inhibiting NFKB, no effects on heat shock protein were found.


Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes 

Zinc carnosine increases gut repair, reduces stress induced gastric and small intestinal injury in rodents and prevents drug induced increases in permeability in humans.


Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats. 

Zinc deficiency is common in alcoholic liver disease. zinc supplementation protected rodents from alcohol induced GI permeability and liver damage.


Magnesium

Progressive magnesium deficiency increases mortality from endotoxin 

Endotoxin administration increases circulating magnesium, higher magnesium status was strongly correlated with increased survival following endotoxin administration.


Magnesium Decreases Inflammatory Cytokine Production: A Novel Innate Immunomodulatory Mechanism 

Magnesium sulfate decreased maternal TNFa and Il-6 and cytokine production in term and preterm neonates.