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Gentamicin-induced renal metabolic alterations in newborn rat kidney: lack of potentiation by vancomycin.

Abstract：

: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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Kacew S,Hewitt WR,Hook JB

doi

10.1016/0041-008x(89)90111-7

subject

Has Abstract

pub_date

1989-06-01 00:00:00

pages

61-71

issue

1

eissn

0041-008X

issn

1096-0333

journal_volume

99

pub_type

杂志文章

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