Potential therapeutic value of lazaroids in endotoxemia and other forms of sepsis.
Lazaroids are developed nonglucocorticoid analogues of methylprednisolone with multiple actions, including the scavenging of reactive oxygen species, the attenuation of inflammation, and the stabilization of biological membranes. In various experimental models, lazaroids were shown to enhance recovery from ischemia-reperfusion injury, central nervous system inflammation, oxidant stress, and panendothelial activation and injury; sepsis might be another important indication for the use of lazaroids. Administration of different lazaroids in experimental endotoxemia and other forms of sepsis indeed showed improvement of biological and hemodynamic parameters, attenuation of inflammation, preservation of oxygenation, and protection of endothelial cell integrity. Further research is needed to determine the effects of these drugs on organ function, mediator synthesis and release, and survival, before appropriate therapeutic protocols for their use in clinical sepsis can be developed.
Spapen
H
H
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
Zhang
H
H
Vincent
J L
JL
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D004727:Endothelium / Q000187:drug effects; D019446:Endotoxemia / Q000188:drug therapy*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008775:Methylprednisolone / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D011281:Pregnatrienes / Q000737:chemistry / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy; D018805:Sepsis / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000975:Antioxidants; D016166:Free Radical Scavengers; D005938:Glucocorticoids; D011281:Pregnatrienes; C074965:U 74389F; D008775:Methylprednisolone; C053355:tirilazad