Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat.
Adenosine antagonists have been previously shown to be of benefit in some ischaemic and nephrotoxic models of acute renal failure (ARF). In the present study, the effects of three alkylxanthines with different potencies as adenosine antagonists 8-phenyltheophylline, theophylline and enprofylline, were examined in rats developing acute renal failure after 4 daily injections of gentamicin (200 mg kg-1). Renal function was assessed by biochemical (plasma urea and creatinine), functional (urine analysis and [3H]inulin and [14C]p-aminohippuric acid clearances) and morphological (degree of necrosis) indices. The various drug treatments produced improvements in some, but not all, measurements of renal function. However, any improvement produced by drug treatment was largely a result of a beneficial effect exerted by its vehicle (polyethylene glycol and NaOH). The lack of any consistent protective effect noted with the alkylxanthines tested in the present study indicates that adenosine plays little, if any, pathophysiological role in gentamicin-induced ARF.
Kellett
R
R
Department of Pharmacology, University of Leeds, UK.
Bowmer
C J
CJ
Collis
M G
MG
Yates
M S
MS
D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003404:Creatinine / Q000097:blood; D005839:Gentamicins / Q000097:blood / Q000633:toxicity* / Q000652:urine; D007668:Kidney / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014508:Urea / Q000097:blood; D014970:Xanthines / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000652:urine
D005839:Gentamicins; D011983:Receptors, Purinergic; D014970:Xanthines; D014508:Urea; D003404:Creatinine; D013806:Theophylline; C028322:8-phenyltheophylline; D000118:Acetylglucosaminidase; D010130:p-Aminohippuric Acid