Protective Effect Of Bg9928, An Adenosine Receptor Antagonist, Against Cisplatin-Induced Acute Renal Injury In Rats: Comparison With Furosemide

Cisplatin (CIS),is nephrotoxic due to renal vasoconstriction and decreased GFR, effects believed to involve of adenosine mediated activation of adenosine A1 receptors (A1Rs). We studied the effect of the A1R antagonist BG9928 (BG) and furosemide (FUR) in CIS-induced acute renal injury in rats. BG was given p.o. at 1mg/kg bid from d0-1 or d0-6, FUR at 30 mg/kg p.o. d0-5 to female SD rats (n=10) pretreated with CIS at 5 or 5.5 mg/kg i.v. Venous blood samples were taken for measurement of creatinine (CRE) and urea nitrogen (BUN) over 13 days. Data was similar for CIS at 5 and 5.5 mg/kg. CIS, 5 mg/kg gave significant elevations in CRE (3.7±0.41 mg/dL), BUN (146.2±18.3 mg/dL) (normal levels: 0.7 ± 0.26 mg/dL CRE & 16.9±2.8 mg/dL BUN) and reduction in body weight.BG d0-1 or d0-6 resulted in significant effects, including limiting accumulation of CRE and BUN to 60% of control, accelerating body weight gain and improved renal histopathology. FUR significantly elevated CRE(5.7±1.3 mg/dL), BUN (207±52 mg/dL) and reduced body weight. All FUR animals died on d7. These data support the involvement of A1Rs in CIS-induced acute renal injury in rats. BG9928 may be useful in the prevention/treatment of renal failure induced by agents like CIS and in other conditions where activation of A1Rs by adenosine in the kidney occurs.