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Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat
R Kellett1, C J Bowmer, M G Collis
1Department of Pharmacology, University of Leeds, UK.
Abstract:
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.
Insights
Adenosine antagonists did not protect against gentamicin-induced acute renal failure (ARF) in rats. The study suggests adenosine plays a minimal role in this specific type of kidney injury.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Adenosine antagonists show promise in models of acute renal failure (ARF).
- Gentamicin is a nephrotoxic antibiotic that can cause ARF.
- Alkylxanthines are adenosine antagonists with varying potencies.
Purpose of the Study:
- To investigate the efficacy of three alkylxanthines (8-phenyltheophylline, theophylline, enprofylline) as adenosine antagonists.
- To determine the role of adenosine in gentamicin-induced ARF in a rat model.
Main Methods:
- Rats received daily gentamicin injections to induce ARF.
- Renal function was assessed using biochemical markers (urea, creatinine), functional tests (urine analysis, clearances), and morphological evaluation (necrosis).
- The effects of alkylxanthine treatments and their vehicles were compared.
Main Results:
- Alkylxanthine treatments showed minor improvements in some renal function parameters.
- These improvements were primarily attributed to the vehicles (polyethylene glycol and NaOH), not the active drugs.
- No consistent protective effect of adenosine antagonists was observed.
Conclusions:
- Adenosine appears to play a limited pathophysiological role in gentamicin-induced ARF.
- Alkylxanthines are not effective in preventing or treating gentamicin-induced kidney injury.
- Further research may be needed to explore other mechanisms in ARF.