my drug doesn't last long (~1hr at best) in the blood stream, so need know how long the lps actually remains there to cause sepsis.
I found that treating my drug (20mg/kg bw; i.p.) after 1hr of LPS (E. coli: O55:B5, 15mg/kg bw; i.p.) made the survival rate 100% up to 33hr and then all the mice in the group died wihtin 60hrs. If LPS lasts long in blood stream then I have to inject my drug at least 3 times at every 1hr after LPS administration.
LPS is removed very quickly from the circulation. within minutes it ends up in the liver.
hope this helps...
LPS has a varying half life in circulating blood lasting from sevaral minutes up to several hours.
The half life of LPS in blood depends on the liver function, because most of the LPS, mosly bound to cells, is removed by kupffer cells in the liver. Even when the LPS can not be detected by LAL test it is often masked by plasmaproteins and still can cause inflammation.
LPS is taken up by all cells that surface express TLR4.and various scavenger receptors. Altho the bulk might end up in the RE System, the receptor is ubiquitously expressed. Further, a certain % of LPS will be immediately bound up and sequestered by lipoproteins , LPS-binding protein, soluble CD14, and several other acute phase proteins, If any of these interactions interfere with your "drug", the intervention could be compromised. Good luck.
Dear Khan! The half-life for LPS is approximately 12 h. Please evaluate the paper in Attachment. Vladimir
The half-life of blood LPS depends on its concentration and functionality of receptors and co-receptors LPS (TLR4, TLR2, CD14, LBP, etc.) in different cells and also liver's ability to remove it.
Please state the object of your study to justify administering even more LPS than you already are doing. Sepsis is not due to LPS per se, but to the many mediators it causes to be released and the organ system failures that occur in consequence. Giving more LPS should not significantly change that outcome or even the time to its onset, although its severity and duration could be affected. Giving more LPS, however, should cause more of it to remain in circulation longer since its clearance by the liver's Kupffer cells and its binding to all its receptors throughout the body should eventually become overwhelmed, given that these can handle only so much LPS until they become saturated.
Dear Dr. Clark, my primary purpose is to develop the appropriate dose of my drug and then will do dose dependency to see how long it can prevent the mortality in mice. Finally, we will conduct the experiment with the defined concentration, dose and a valid time-frame.
My cordial gratitude goes for everyone.
The circulating half-life and the pharmacodynamic half-life of LPS may be different, so even while it is in circulation it may not be active. Researchers who have studied the LAL reactivity of LPS have found that its reactivity disappears over time while it sits in plasma. There are studies done in humans that describe the activity of LPS after injection. In most cases, when 4 ng/kg is injected, physiological changes are seen within 20-30 min, and flu-like symptoms are observed for about 4 hours. so what you see at 12 hours is not likely LPS. Concomitant injection of E5564 with LPS blocks all symptoms, even with doses of E5564 that have about a 20 minute half-life.. so the activity of LPS has to have a half-life of 20 minutes or less. Of course much higher doses of LPS will "stick atound" longer, but you should not be using much more than threshold doses of LPS to get the effects you want to see.
Endotoxin release is episodic and circulating LPS has a short half-life (minutes), obscuring the value of a single determination. In the bloodstream, LPS is distributed in varying proportions bound by LBP, micelles, chylomicrons, and various other lipid fractions; some of these bound moieties are biologically inactive, but most assays measure all LPS whether biologically active or not—again, making the relevance of the results uncertain.
http://www.biostrategics.com/kpmgendo.pdf
.....Endotoxin release is episodic and circulating LPS has a short half-life (minutes), obscuring the value of a single determination. In the bloodstream, LPS is distributed in varying proportions bound by LBP, micelles, chylomicrons, and various other lipid fractions; some of these bound moieties are biologically inactive, but most assays measure all LPS whether biologically active or not—again, making the relevance of the results uncertain.
.....The susceptibility of different animal species to the toxicity of lipopolysaccharide (LPS) is highly variable.
http://www.biostrategics.com/kpmgendo.pdf
https://www.researchgate.net/post/Does_lipopolysachharide_LPS_has_any_defined_half-life#56eb0a32eeae39131d1a8d01
Mustafa is right, and the "real endotoxin" as it is shed from bacteria, is heterogeneous in structure, and likely aggregated in various forms, so fractional binding to different proteins and lipoproteins is probably not cleanly predictable.
This paper shows 2-4 minutes in mice.
Article Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Live...
The half-life of lipopolysaccharide (LPS) in the bloodstream is not well defined. It can vary depending on a number of factors, including the dose, route of administration, and the presence of other medications or treatments. However, LPS can persist in the bloodstream for several hours to several days.
To determine the half-life of LPS more precisely, you could perform additional studies using methods such as blood sampling at regular intervals after LPS administration and measuring the levels of LPS in the bloodstream using techniques such as ELISA or mass spectrometry.
If you want to maximize the effectiveness of your drug, it may be a good idea to administer it multiple times at 1-hour intervals after LPS administration, as you suggested.
The release of LPS from bacteria is indeed episodic and the circulating LPS has a very short half-life of just a few minutes. The measurement of LPS in the bloodstream can be challenging due to its rapid clearance and the fact that it is distributed in varying proportions bound by various lipid fractions, some of which may be biologically inactive. This can make it difficult to determine the relevance and significance of LPS levels in the bloodstream.
Additionally, the susceptibility of different animal species to the toxicity of LPS is highly variable. This variability can make it challenging to extrapolate results from animal studies to humans, highlighting the importance of carefully considering the species used in studies when interpreting the results.
These complexities highlight the need for careful consideration and interpretation of the results when measuring LPS levels in the bloodstream and the importance of using multiple, complementary methods to study LPS and its role in sepsis and other diseases.