Lysophosphatidylcholine reduces the organ injury and dysfunction in rodent models of gram-negative and gram-positive shock.
1. Lysophosphatidylcholine (LPC) modulates the inflammatory response and reduces mortality in animal models of sepsis. Here, we investigate the effects of LPC from synthetic (sLPC) and natural, soy bean derived LPC, (nLPC) sources on the organ injury/dysfunction caused by systemic administration of lipopolysaccharide (LPS) or peptidoglycan (PepG) and lipoteichoic acid (LTA). 2. Rats were subjected to (i) endotoxaemia (LPS 6 mg kg(-1) i.v.) and treated with sLPC (1-100 mg kg(-1)), (ii) endotoxaemia and treated with nLPC (10 mg kg(-1)) or (iii) gram-positive shock (PepG 10 mg kg(-1) and LTA 3 mg kg(-1) i.v.) and treated with sLPC (10 mg kg(-1)). 3. Endotoxaemia or gram-positive shock for 6 h resulted in increases in serum makers of renal dysfunction and liver, pancreatic and neuromuscular injury. 4. Administration of sLPC, at 1 or 2 h after LPS, dose dependently (1-10 mg kg(-1)) reduced the organ injury/dysfunction. High doses of sLPC (30 and 100 mg kg(-1)) were shown to be detrimental in endotoxaemia. sLPC also afforded protection against the organ injury/dysfunction caused by gram-positive shock. nLPC was found to be protective in endotoxaemic animals. 5. The beneficial effects of sLPC were associated with an attenuation in circulating levels of interleukin-1beta (IL-1beta). 6. In conclusion, LPC dose and time dependently reduces the organ injury and circulating IL-1beta levels caused by gram-negative or gram-positive shock in the rat. Thus, we speculate that appropriate doses of LPC may be useful in reducing the degree of organ injury and dysfunction associated with shock of various aetiologies.
Murch
Oliver
O
The Centre for Experimental Medicine, Nephrology and Critical Care, The William Harvey Research Institute, St Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ.
Collin
Marika
M
Sepodes
Bruno
B
Foster
Simon J
SJ
Mota-Filipe
Helder
H
Thiemermann
Christoph
C
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008244:Lysophosphatidylcholines / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy*; D013997:Time Factors
D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines