Acute protective effects of simvastatin in the rat model of renal ischemia-reperfusion injury: it is never too late for the pretreatment.
Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg/kg) significantly protects rat kidney injured by ischemia-reperfusion (I/R) (45 min + 6 h). We aimed to determine the optimal timing of such a pretreatment. The effects of both injections of simvastatin before ischemia and reperfusion were similar regarding total histological score. However, simvastatin injected 30 min before ischemia was 30% - 75% more effective in reduction of serum creatinine levels and interstitial edema score, while its injections 5 and 30 min before reperfusion were 25% - 60% more effective in reduction of tubular necrosis score and fractional excretion of Na+. However, the observed differences do not seem to offer significant advantage in clinical settings.
Todorovic
Zoran
Z
Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia.
Nesic
Zorica
Z
Stojanović
Radan
R
Basta-Jovanović
Gordana
G
Radojevic-Skodrić
Sanja
S
Velicković
Ruzca
R
Chatterjee
Prabal K
PK
Thiemermann
Christoph
C
Prostran
Milica
M
D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D012964:Sodium / Q000652:urine; D013997:Time Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012964:Sodium; D019821:Simvastatin; D003404:Creatinine