Gentamicin-induced renal metabolic alterations in newborn rat kidney: lack of potentiation by vancomycin.
Daily subcutaneous administration of 20 or 100 mg/kg gentamicin for 4 days significantly decreased pyridoxal-5'-phosphate and lysosomal specific phosphatidylinositol-phospholipase C (PI-PLC) in newborn rat kidney. The fall in PI-PLC was associated with an elevation in renal phosphatidylinositol, phosphatidylserine, and phosphatidylcholine. The 100 mg/kg gentamicin dose also produced a rise in renal sphingomyelin, phosphatidylethanolamine, phosphatidylglycerol, and total phospholipid (TPL) accompanied by inhibition in the activities of Na+,K+-ATPase and alkaline phosphatase. In contrast, daily intraperitoneal injection of 100 mg/kg vancomycin for 4 days failed to markedly alter renal metabolic parameters. However, the 500 mg/kg vancomycin dose increased kidney weight, TPL, and all individual phospholipid class concentrations accompanied by inhibition of lysosomal specific PI-PLC activity and reduced pyridoxal-5'-phosphate levels. Simultaneous administration of 20 mg/kg gentamicin with either vancomycin dose resulted in renal alterations similar to those produced by gentamicin alone. Concurrent treatment with 100 mg/kg aminoglycoside and either vancomycin dose produced changes in kidney which were similar to those produced by gentamicin alone, except for a synergistic rise in PI as well as a greater fall in alkaline phosphatase and pyridoxal-5'-phosphate. Surprisingly, the concentration of gentamicin and vancomycin was less in newborn kidneys of rats receiving a simultaneous high dose of vancomycin and aminoglycoside treatment compared to levels found in animals given either antibiotic separately. The lack of potentiation of nephrotoxicity in newborns administered a combination of vancomycin and gentamicin may be due to decreased accumulation of either antibiotic in kidney.
Kacew
S
S
Department of Pharmacology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
Hewitt
W R
WR
Hook
J B
JB
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D010743:Phospholipids / Q000032:analysis; D011732:Pyridoxal Phosphate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000378:metabolism; D014640:Vancomycin / Q000633:toxicity*
D005839:Gentamicins; D010743:Phospholipids; D011732:Pyridoxal Phosphate; D014640:Vancomycin; D000469:Alkaline Phosphatase; D010738:Type C Phospholipases; D000251:Adenosine Triphosphatases