Pre-treatment with high density lipoprotein (HDL) attenuates the renal and hepatic dysfunction caused by endotoxin in rats

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Introduction High-density lipoprotein (HDL) binds to lipopolysaccharide1 (LPS), has anti-inflammatory properties2 and exerts beneficial effects in some, but not all, models of endotoxaemia.3 Here we investigate the effects of HDL on the multiple organ injury and dysfunction caused by endotoxin in the rat. Methods: Male Wistar rats (n = 33) were anaesthetized with sodium thiopental (120 mg kg−1 i.p.) and instrumented for the measurement of blood pressure. At 30 min after surgery, animals were pre-treated with HDL (80 mg kg−1 i.v.,n = 9) or with saline (4 ml kg−1 iv,n = 10) and 5 min later they receivedE. coli LPS (6 mg kg−1 i.v) as a slow injection over 20 min. In addition, two groups of rats which had received vehicle rather than LPS (sham-operated animals) were also pre-treated with either HDL (n = 4) or saline (n = 6). All rats received an infusion of saline (1.5 ml kg−1 h−1). Results: Four out of 14 rats treated with saline and 0 out of 9 rats treated with HDL died within 6 h of administration of LPS and were excluded from further analysis. Endotoxaemia caused a bi-phasic fall in blood pressure as well as liver and pancreatic injury (determined by serum levels of AST, ALT and lipase) and renal dysfunction (increase in serum levels of urea and creatinine). Pre-treatment of rats with HDL significantly attenuated the renal and hepatic injury (P Conclusion Pretreatment with HDL attenuates the renal and hepatic injury/dysfunction associated with severe endotoxin shock in the rat. The mechanism of this beneficial effect of HDL warrants further investigation.