Prostaglandins and aminoglycoside nephrotoxicity

B. M. Assael, C. Chiabrando, L. Gagliardi, A. Noseda, F. Bamonte, M. Salmona

Research output: Contribution to journalArticlepeer-review

Abstract

The role of prostaglandins in the development of aminoglycosideinduced acute renal failure was studied in CD-COBS rats (200 to 250 g). The animals were treated with gentamicin (80 mg/kg), acetylsalicylic acid (ASA, 100 or 200 mg/kg), or both drugs or saline for 5 or 10 days. Renal function was studied measuring creatinine clearance, blood urea nitrogen (BUN), and serum electrolytes, urine osmolality, and maximal urinary concentrating capacity after water deprivation and vasopressin administration. Gentamicin toxicity on the proximal tubule was evaluated by measuring urinary excretion of the lysosomal enzyme N-acetylglucosaminidase (NAG). Renal prostaglandin (PG) production was evaluated measuring the concentration of PGE2, PGD2, PGF, 6-keto-PGF, and thromboxane B2 (TXB2) in whole renal homogenate after a 15-min incubation at 37°C using gas chromatographymass spectrometry. Gentamicin alone reduced the glomerular filtration rate (GFR) 20 to 30% after 5 and 10 days of treatment. Combination with ASA protentiated the toxic effect of the aminoglycoside after 10 but not after 5 days of treatment. Similarly, gentamicin reduced the urinary concentrating capacity and addition of ASA worsened the effects. Gentamicin markedly increased NAG excretion but this effect was reduced by ASA, probably as a result of lysosomal stabilization. ASA alone inhibited the production of prostaglandins in renal tissue by 70 to 90% after single or multiple doses. The animals treated with gentamicin alone presented a significant, specific increase in PGE2 production after 10 days of treatment but this increase did not occur when the two compounds were given together. Since PGE2 has a vasodilatory effect in the kidney these results suggest that it may play a specific role in maintaining normal renal blood flow and GFR during the development of aminoglycoside nephrotoxicity. The inhibition of prostaglandin production by nonsteroid anti-inflammatory drugs prevents this compensatory mechanism and worsens the renal damage.

Original languageEnglish
Pages (from-to)386-394
Number of pages9
JournalToxicology and Applied Pharmacology
Volume78
Issue number3
DOIs
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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