Effect of tempol, a membrane-permeable radical scavenger, on mesenteric blood flow and organ injury in a murine cecal ligation and puncture model of septic shock.
BACKGROUND
Interventions that reduce the generation or the effects of reactive oxygen species exert beneficial effects in a variety of models of septic shock. We investigated the effect of tempol, a low-molecular-weight membrane-permeable radical scavenger, on mesenteric blood flow and organ injury in a murine cecal ligation and puncture (CLP) model of septic shock.


METHODS
Forty-four Swiss albino mice were anesthetized with chloral hydrate (400 mg/kg, i.p.) and subjected to CLP (except for the sham-operated animals). The animals were divided randomly into 4 groups: the 1st group was sham operated (sham-operated group, n = 10); the 2nd group underwent CLP and was injected with saline (CLP + saline group, n = 12); the 3rd group was sham operated and treated with tempol (10 mg/kg, i.p., sham-treated + tempol group, n = 10); the 4th group underwent CLP and was treated with tempol (10 mg/kg, i.p., CLP + tempol group, n = 12). Mesenteric arterial blood flow (MABF) was measured by Doppler ultrasound. Poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) activity was examined in the liver, lung, and kidneys.


RESULTS
In the CLP + saline group, the MABF was significantly lower than in the sham-operated group (p < 0.001). After tempol administration, MABF values significantly increased (p < 0.05). We observed significantly stronger PARP-positive staining in the lungs and kidney glomeruli in the CLP + saline group than in those of the sham-operated group (p(lung) = 0.0148, p(glomeruli) = 0.0025). A marked reduction in PARP activity was found in the lung and kidney glomeruli of the CLP + tempol group (p(lung) = 0.0026, p(glomeruli) = 0.0085). There was no significant effect of CLP on PARP activity in the liver and kidney tubuli (p(liver) > 0.05, p(tubuli) > 0.05).


CONCLUSIONS
Tempol improved MABF in a CLP-induced septic shock model. Although tempol could not prevent the activation of PARP in the liver and kidney tubuli, it did attenuate PARP activation in the lung and kidney glomeruli.
Yuksel
B C
BC
First Department of Surgery, Ministry of Health, Ankara Numune Research and Training Hospital, Ankara, Turkey. bulentcyuksel@yahoo.com.tr
Serdar
S E
SE
Tuncel
A
A
Uzum
N
N
Ataoglu
O
O
Atan
A
A
Hengirmen
S
S
Iskit
A B
AB
Guc
M O
MO
D000818:Animals; D002432:Cecum; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D009102:Multiple Organ Failure / Q000517:prevention & control; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011677:Punctures; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D013113:Spin Labels; D013152:Splanchnic Circulation / Q000187:drug effects*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D011065:Poly(ADP-ribose) Polymerases; C001803:tempol