Effects of olprinone, a phosphodiesterase III inhibitor, on ischemic acute renal failure.
OBJECTIVE
Renal ischemic reperfusion injury (IRI) is unavoidable and is still one of the major problems in renal transplantation. The aim of this study was to investigate the effects of olprinone, a phosphodiesterase III inhibitor, on renal IRI.


METHODS
After a right nephrectomy, renal IRI was induced in rats. Olprinone was given in two different ways: sustained systemic administration and transient local administration to the kidney. Control rats were treated with saline. Using a magnifying endoscope, the renal blood flow speed was measured at 23 h after reperfusion. Then, blood samples were collected, and kidney specimens were taken for histological study. In order to study the mechanism, we performed in vitro experiments, using human proximal renal tubular cells (HK-2) incubated with tumor necrosis factor (TNF)-alpha along with olprinone or saline, and interleukin (IL)-8 was measured in the culture supernatant.


RESULTS
In the saline group, the blood flow speed (BFS) was greatly reduced compared to that in normal kidneys. In both olprinone-treated groups, BFS of the renal microcirculation significantly increased, tubular damage and macrophage infiltration attenuated, and renal function greatly improved. Olprinone inhibited the increase in the IL-8 levels resulting from the incubation of HK-2 with TNF-alpha.


CONCLUSIONS
Our study successfully demonstrates that olprinone has renoprotective properties when applied locally as well as systemically. The results suggest that olprinone might be clinically useful in renal transplantation for the donor kidney, the recipient, and even in treating acute renal failure.
Anas
Chabouk
C
Departments of Urology and Nephrology, Nagoya University Graduate School of Medicine, 65 Tsusumaicho, Showaku, Nagoya, Aichi, Japan.
Ozaki
Takenori
T
Maruyama
Shoichi
S
Yamamoto
Tokunori
T
Zu Gotoh
Momoka
M
Ono
Yoshinari
Y
Matsuo
Seiichi
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000097:blood; D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D001806:Blood Urea Nitrogen; D002478:Cells, Cultured; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018715:Microscopy, Video; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome
D007093:Imidazoles; D016209:Interleukin-8; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3