Amphotericin B and sodium deoxycholate induced impairment of renal p-aminohippurate accumulation (PAH) and effect on lipid peroxidation in the rat kidney.
The influence of amphotericin B on PAH transport as well as on lipid peroxidation in rat renal cortical slices was studied in vitro and ex vivo. In vitro, renal cortical slices were incubated with different amphotericin B (AmB) concentrations (2-60 micrograms/mL) or with the corresponding vehicle concentrations of sodium deoxycholate (NaDo) (1.64-49.2 micrograms/mL) and time dependently (15-30-60 min) with 30 micrograms/mL AmB or 24.6 micrograms/mL NaDo. Ex vivo, PAH transport of renal cortical slices was investigated following a 3-day intravenous AmB administration with 3 mg/kg per day or 2.46 mg/kg/day NaDo, respectively. In vitro AmB as well as NaDo decreased PAH transport dose and time dependently. At the highest AmB concentration of 60 micrograms/mL, PAH uptake decreased to 17.6%. The corresponding NaDo concentration (49.2 micrograms/mL) decreased PAH uptake to 33.3%. Time dependently AmB decreased PAH uptake to 25% after 60 min. NaDo caused a decrease to 69%. Administration of AmB for 3 days resulted in a PAH decline to 81%; NaDO decreased PAH uptake to 77%. In vitro as well as in vivo, AmB or its vehicle did not induce lipid peroxidation in renal cortical tissue. In summary, the results show that AmB and its vehicle, NaDo, decrease PAH uptake by renal cortical cells, reflecting a direct effect of AmB on tubular function. The impairment of the PAH transport is not due to enhanced lipid peroxidation.
Inselmann
G
G
1. Medizinische Klinik, Christian-Albrechts-Universität Kiel, Germany.
Kutzschbach
A
A
Heidemann
H T
HT
D000666:Amphotericin B / Q000009:adverse effects*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003840:Deoxycholic Acid / Q000009:adverse effects*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D003840:Deoxycholic Acid; D000666:Amphotericin B; D010130:p-Aminohippuric Acid