The effects of the nonsteroidal anti-inflammatory drug diclofenac sodium on the rat kidney, and alteration by furosemide.
BACKGROUND
Renal physiology is a partially cyclooxygenase (COX)-dependent system. Kidneys express both COX-1 and COX-2 enzymes. In this study, we tried to investigate the effects of diclofenac sodium (D), with or without furosemide (F), on plasma renin activity (PRA), serum and urine electrolytes, creatinine clearance, and COX-1 and COX-2 expression in the renal cortex.


METHODS
Forty-two Wistar-albino rats were divided into four groups (G). G1, G2, G3, and G4 were treated with placebo, F (20 mg/kg), F (20 mg/kg) plus D (2.5 mg/kg), and D (2.5 mg/kg), respectively, and followed for seven days. Urinary osmolality and volume, and levels of serum and urinary creatinine, sodium, and potassium were measured. Renal COX-1 and COX-2 expression were examined by the immunohistochemical method.


RESULTS
Compared with G1, body weights were significantly reduced in G3 and G4 (P < 0.05 for all). Serum sodium in G2 decreased significantly compared with G1, G3, and G4. Serum potassium in G2 decreased significantly compared with G1 and G3. Urine volume in G2 increased significantly compared with G1, G3, and G4. Urine osmolality in G2 and G4 decreased significantly compared with G1 and G3. Urine Na in G2 increased significantly compared with G4. Although urine K was lowest in G4, there were no statistically significant differences between the groups. Creatinine clearance decreased in G4 compared with the other groups. PRA was similar in all groups. Renal cortical COX-2 expression was lowest in G1. COX-1 expression in cortical collecting tubules was significantly reduced in G3 and G4 compared with G1 and G2 (P < 0.05 for all). Although creatinine clearance in G4 was significantly lower than in G3, COX-1 and COX-2 expression were no different in G3 and G4.


CONCLUSIONS
Acute renal failure was caused by D. F prevented development of renal failure in rats treated with a combination of D and F. The diuretic effect of F was neutralized by D. Whereas COX-1 expression was reduced by D and by the combination of D and F in G3 and G4, renal COX-2 immunoreactivity was increased by F and D and the combination of both. Although creatinine clearance was lower in rats that were given D alone compared with the combination of F and D, COX-1 and COX-2 expression were similar in these groups.
Besen
Ayberk
A
Faculty of Medicine, Department of Nephrology, Cukurova University, Adana, Turkey.
Kose
Fatih
F
Paydas
Saime
S
Gonlusen
Gulfiliz
G
Inal
Tamer
T
Dogan
Ayse
A
Kibar
Mustafa
M
Balal
Mustafa
M
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D001707:Biopsy, Needle; D003404:Creatinine / Q000652:urine; D051545:Cyclooxygenase 1 / Q000032:analysis / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism; D004008:Diclofenac / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D016482:Urinalysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D005665:Furosemide; D003404:Creatinine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2