Allopurinol fails to protect against gentamicin-induced renal damage in normotensive and spontaneously hypertensive rats.
Recent research suggests the involvement of hydroxyl and superoxide free radicals in the development of gentamicin-induced acute renal tubular necrosis. Xanthine oxidase has been implicated as an important source of superoxide free radicals. Spontaneously hypertensive (Wistar-Kyoto) rats (SHR) have excessive oxidant stress which may render them more sensitive to the proported oxygen free radical producing effects of gentamicin. This study was undertaken to determine if the xanthine oxidase inhibitor allopurinol will ameliorate the effects of gentamicin. Normotensive Wistar-Kyoto (WKY) rats and SHR were administered allopurinol (40 mg/kg twice daily) orally 4 days before and throughout a 12-day gentamicin treatment period. The allopurinol only treatment group demonstrated no noticeable histological or functional changes considered to be indicative of nephrotoxicity. Gentamicin-injected WKY rats and SHR equally demonstrated extensive proximal tubular and glomerular damage characteristic of aminoglycoside-induced kidney damage. Allopurinol failed to protect either rat strain against the histological damage caused by gentamicin. Equivalent alterations in serum creatinine, serum gentamicin, urinary N-acetyl-beta-D-glucosaminidase excretion, body weight, urinary output, and blood pressure occurred in the gentamicin with allopurinol and gentamicin only treatment groups. Our results demonstrate allopurinol does not ameliorate the pathogenesis of gentamicin. SHR do not appear to be more sensitive to the effects of gentamicin induced kidney damage with or without allopurinol as compared with WKY rats.
Smyth
B J
BJ
Department of Pathology, Medical University of South Carolina, Charleston 29425-2645.
Davis
W G
WG
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D005839:Gentamicins / Q000633:toxicity*; D006977:Hypertension, Renal / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D005839:Gentamicins; D000493:Allopurinol; D010100:Oxygen