Related Experiment Videos
Apoptosis contributes to amphotericin B-induced nephrotoxicity
D E Varlam1, M M Siddiq, L A Parton
1Department of Pediatrics, SUNY at Stony Brook, Stony Brook, New York 11794-8111, USA.
Antimicrobial Agents and Chemotherapy
|February 22, 2001
Summary
Amphotericin B (AmB) causes kidney damage by inducing apoptosis, or programmed cell death. Co-administration with insulin-like growth factor-1 (IGF-1) effectively prevents this AmB-induced nephrotoxicity in rats.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Amphotericin B (AmB) is a vital antifungal agent but is associated with significant nephrotoxicity.
- The precise mechanisms underlying AmB-induced kidney damage require further elucidation.
Purpose of the Study:
- To investigate the role of apoptosis in Amphotericin B-induced nephrotoxicity.
- To evaluate the protective effect of recombinant human insulin-like growth factor-1 (rhIGF-1) against AmB-induced kidney damage.
Main Methods:
- In vitro studies using proximal tubular (LLC-PK(1)) and medullary interstitial (RMIC) cells treated with AmB.
- In vivo studies using Sprague-Dawley rats treated with AmB, with and without rhIGF-1.
- Assessment of apoptosis via DNA fragmentation and microscopic examination of renal tissues.
Main Results:
- AmB induced apoptosis in renal cells in vitro.
- In vivo, AmB caused dose-dependent nephrotoxicity, including hypokalemia, weight loss, and impaired renal function, accompanied by apoptotic alterations in tubular epithelial cells.
- Concomitant administration of rhIGF-1 abrogated AmB-induced apoptosis and prevented clinical signs of nephrotoxicity.
Conclusions:
- Amphotericin B induces nephrotoxicity through a dose-dependent apoptotic pathway in the rat kidney.
- Recombinant human insulin-like growth factor-1 demonstrates a protective effect against AmB-induced nephrotoxicity by inhibiting apoptosis.