The effects of nonsteroidal anti-inflammatory drug, diclofenac, upon the rat kidney and the alterations with furosemid

Renal physiology is partially cyclooxygenase (COX) dependent. Prostaglandinsare active in regulating vascular tone and salt and water homeostasis by modulatingglomerular hemodynamics and regulating distal nephron function. Unlike thegastrointestinal tract and platelets in which physiological function depends oncyclooxygenase-1 (COX-1) kidneys express COX-1 and cyclooxygenase -2 (COX-2).In this experimental study our aim was to investigate the effects of nonselectivenonsteroidal anti-inflammatory drug diclofenac sodium alone and with a loop diureticfurosemide on renal functions, plasma renin activity (PRA) and COX-1 and COX-2expression at renal cortex.Forty two Wistar-Albino rats were used in the study. Rats were divided to 4groups. Group 1 (G1), group 2 (G2), group 3 (G3) and group 4 (G4) were givenplacebo, furosemide (20 mg/kg), furosemide (20 mg/kg) plus diclofenac sodium (2,5mg/kg) and diclofenac sodium (2,5 mg/kg) respectively. At the end of the study, bloodurea nitrogen and serum creatinin levels were not different between groups but in G4creatinin clearence was significantly lower than other 3 groups (p<0.05). PRA was notdifferent between groups. COX-1 immunoreactivity in G1 and G2 was similar.Diclofenac sodium decreased COX-1 immunoreactivity at renal cortex (p<0.05). COX-2 immunoreactivity increased both with diuretic and diclofenac sodium (p<0.05).Finally, acute renal failure developed with diclofenac sodium at 2,5 mg/kg/daydosage, and furosemide prevented renal failure development in rats trated withcombination of diclofenac sodium and furosemid. Diuretic, natriuretic and kaliureticeffects of furosemide was neutralised by diclofenac sodium. Renal COX-1immunoreactivity did not change with furosemide but decreased with diclofenacsodium. Renal COX-2 immunoreactivity increased with both furosemide anddiclofenac sodium. There was no relationship between development of renal failure andCOX-1 and COX-2 expression.Key Words: COX-1 immunoreactivity, COX-2 immunoreactivity, Diclofenac sodium.