Effects of celecoxib and nordihydroguaiaretic acid on puromycin aminonucleoside-induced nephrosis in the rat.
The selective cyclooxygenase-2 (COX-2) and 5-lipoxygenase (LOX) inhibitors might inhibit prostaglandin synthesis and reduce proteinuria. The present study was designed to investigate the anti-proteinuric effects of nordihydroguaiaretic acid (NDGA) as compared with celecoxib in puromycin aminonucleoside (PAN) nephrosis rats. Fifty five male Sprague-Dawley rats were divided into 4 groups; A, normal control; B, PAN group; C, PAN+COX-2 inhibitor (celecoxib) group; and D, PAN+5-LOX inhibitor (NDGA) group. After induction of PAN nephrosis through repeated injections of PAN (7.5 and 15 mg/100 g body weight), rats were treated with celecoxib, NDGA, or vehicle for 2 weeks. Twenty four hour urine protein excretions were significantly lower in PAN+celecoxib and PAN+NDGA groups than in PAN group. Serum creatinine (SCr) concentrations and 24 hr urine creatinine clearances (CCr) were not significantly different in the four groups. Electron microscopy showed that podocyte morphology was changed after the induction of PAN nephrosis and was recovered after celecoxib or NDGA administration. Celecoxib significantly recovered the expressions of nephrin, CD2AP, COX-2, and TGF-beta. NDGA also recovered TGF-beta expression, but did not alter the expressions of nephrin, CD2AP and COX-2. The present study suggested that celecoxib and NDGA might effectively reduce proteinuria in nephrotic syndrome without impairing renal function.
Lee
Dong Won
DW
Department of Internal Medicine, Pusan National University School of Medicine, Seo-gu, Busan, Korea.
Kwak
Ihm Soo
IS
Lee
Soo Bong
SB
Song
Sang Heon
SH
Seong
Eun Young
EY
Chung
Hyun Chul
HC
Yang
Byeong Yun
BY
Lee
Min Young
MY
Sol
Mee Young
MY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001835:Body Weight; D000068579:Celecoxib; D003404:Creatinine / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D008854:Microscopy, Electron; D009401:Nephrosis / Q000139:chemically induced* / Q000188:drug therapy; D050199:Podocytes / Q000378:metabolism; D011692:Puromycin Aminonucleoside / Q000494:pharmacology / Q000633:toxicity*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D011692:Puromycin Aminonucleoside; D009637:Masoprocol; D003404:Creatinine; D000068579:Celecoxib