Abstract:
BACKGROUND/AIMS:Cisplatin (CIS) induces nephrotoxicity partly through renal vasoconstriction and decreased glomerular filtration effects thought to involve adenosine acting on adenosine A(1) receptors (A1Rs). We studied the effect of the orally active, A1R antagonist tonapofylline (BG9928) on biochemical measures of renal function in CIS-induced acute kidney injury (AKI) in rats. METHODS:Tonapofylline, 1 mg/kg b.i.d., p.o., was administered on days 0-1 or 0-6 to rats treated with CIS 5.5 mg/kg i.v. Prednisolone (PRED) 5 mg/kg s.c. (day 0) served as a positive control. Serum creatinine and urea nitrogen (BUN) were measured in serial blood samples taken over the 13-day study period. RESULTS:CIS produced significant elevations in creatinine, reduction in body weight and marked proximal tubular injury throughout the renal cortex and outer medulla. Tonapofylline, days 0-1 or 0-6 and PRED all produced sustained reductions in post-CIS serum creatinine and BUN levels compared with controls, improved body weight recovery and significant attenuation of CIS-induced kidney pathology scores. CONCLUSION:These data support the involvement of A1Rs in CIS-induced AKI in rats. Tonapofylline may be useful in the clinical setting for the prevention of kidney failure induced by nephrotoxic agents such as CIS.
journal_name
Am J Nephroljournal_title
American journal of nephrologyauthors
Gill A,Wortham K,Costa D,Davis W,Ticho B,Whalley Edoi
10.1159/000248762subject
Has Abstractpub_date
2009-01-01 00:00:00pages
521-6issue
6eissn
0250-8095issn
1421-9670pii
000248762journal_volume
30pub_type
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journal_title:American journal of nephrology
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