Amphotericin B and amphotericin B methylester: effect on brush border membrane permeability

Area of Science:

• Nephrology
• Pharmacology
• Biochemistry

Background:

• Polyene antibiotics like Amphotericin B (AM) are known for nephrotoxicity.
• Previous studies on AM's mechanism were confounded by the use of sodium deoxycholate (DOC) solvent.
• A water-soluble derivative, methylester aspartate salt of Amphotericin B (AME), was developed to avoid organic solvents.

Purpose of the Study:

• To investigate the effect of AM, DOC, and AME on kidney tubule membrane permeability.
• To elucidate the specific action of AME on sodium transport in renal brush border membranes.

Main Methods:

• Utilized rat kidney cortex brush border membrane (BBM) vesicles.
• Measured 22Na uptake using a rapid filtration technique.
• Assessed 22Na and 3H-D-mannitol efflux from BBM vesicles under various AME concentrations and preincubation times.

Main Results:

• Both AM and AME significantly increased 22Na uptake across BBM vesicles.
• A substantial portion of AM's effect was attributed to the solvent DOC.
• AME demonstrated a dose-dependent increase in 22Na efflux, with no effect on mannitol efflux, indicating specific ion channel activity.

Conclusions:

• AME increases sodium permeability of renal brush border membranes.
• The findings suggest AME's potential role in Amphotericin B-induced nephrotoxicity.
• AME offers a tool to study membrane transport independent of organic solvents.