Lysophosphatidylcholine reduces the organ injury and dysfunction in rodent models of Gram‐negative and Gram‐positive shock

Abstract

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). 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). Endotoxaemia or Gram‐positive shock for 6 h resulted in increases in serum makers of renal dysfunction and liver, pancreatic and neuromuscular injury. 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. The beneficial effects of sLPC were associated with an attenuation in circulating levels of interleukin‐1β (IL‐1β). In conclusion, LPC dose and time dependently reduces the organ injury and circulating IL‐1β 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. British Journal of Pharmacology (2006) 148, 769–777. doi:

The synthetic bile acid–phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide suppresses TNFα-induced liver injury

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Monitoring mmp-9 gene expression in stromal cells using a novel transgenic mouse model

“…We found that LPS injection (50 mg/kg) induced a consistent and significant increase in bioluminescent signals in the liver (Fig. 2a), which is a major target of LPS-induced septic shock [13]. No significant or consistent increase in bioluminescence was found in the other organs, such as the spleen, the kidneys, the lung, and the thymuses, following LPS injection.…”

“…Functional analysis of the mmp-9 promoter transgene MMP-9 gene expression is regulated by a number of different stimuli in different cell types, most notably by LPS in liver and kidney tissues [11][12][13]. To determine whether our transgene model may be used to assess the activation of the mmp-9 promoter by inflammatory mediators using bioluminescence imaging, we injected Tg and control mice with LPS.…”

Immunomodulatory Actions of Lysophosphatidylcholine

“…LPC administration inhibited LPS-or cecal ligation and puncture (CLP)-induced increase in plasma HMGB1 levels in mice (Chen et al, 2005). Furthermore, LPC administration inhibited LPS-or peptidoglycan/lipoteichoic acid-induced multiple organ damage in rats (Murch et al, 2006).…”