Decline in the expression of copper/zinc superoxide dismutase in the kidney of rats with endotoxic shock: effects of the superoxide anion radical scavenger, tempol, on organ injury.
1. Endotoxaemia causes an enhanced formation of reactive oxygen species (ROS) which contribute to the multiple organ dysfunction syndrome (MODS) in septic shock. Here we investigate (i) the effects of endotoxin on the expression of two isoforms of superoxide dismutase (SOD), namely Cu/Zn-SOD (cytosol) and Mn-SOD (mitochondria) in the rat kidney, and (ii) the effects of the radical scavenger tempol on the MODS caused by lipopolysaccharide (LPS, E. coli, 6 mg kg(-1) i.v.) in the rat. 2. Endotoxaemia resulted in a rapid, but transient, decline in the expression of both mRNA and protein of Cu/Zn-SOD as well as an increase in the expression of the mRNA of Mn-SOD in the kidney. Endotoxaemia for 6 h also caused hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury and an increase in the plasma levels of nitrite/nitrate. 3. Pretreatment of rats with tempol (100 mg kg(-1) i.v. bolus injection, 15 min prior to LPS followed by an infusion of 30 mg kg(-1) i.v., n=9) did not affect the circulatory failure, but attenuated the renal dysfunction and the hepatocellular injury/dysfunction caused by LPS. Tempol did not affect the rise in nitrite/nitrate caused by endotoxin. 4. These results imply that an enhanced formation of ROS (including superoxide anions) in conjunction with inadequate defences against such ROS contributes to the injury and dysfunction of the kidney and the liver in endotoxic shock.
Leach
M
M
The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, UK.
Frank
S
S
Olbrich
A
A
Pfeilschifter
J
J
Thiemermann
C
C
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D019446:Endotoxemia / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000293:injuries / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012313:RNA / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012260:Ribonucleases / Q000187:drug effects; D012772:Shock, Septic / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013481:Superoxides; D012313:RNA; D013482:Superoxide Dismutase; D012260:Ribonucleases; C001803:tempol