Amp-B induced renal toxicity and electrolyte losses limit treatment of fungal sepsis. In vitro, interstitial, proximal, and distal tubular cells respond with AP following exposure to AmpB. Moreover, IGF-I prevents DNA fragmentation in renal cell lines treated with AmpB. This study investigated the induction of AP by AmpB in vivo, and the ability of IGF-I to prevent this effect. Sixteen three week old male Sprague-Dawley rats were randomized into eight groups. Rats were treated with AmpB at 5, 10 or 15 mg/kg i.p. qd × 5; ± IGF-I at 4mg/kg s.c. qd × 5. One control group received D5W i.p. and a second control group IGF-I s.c.. The rats were weighed daily and urine specific gravities (SG) were measured. The D5W control group gained 10% of their body weight daily. The IGF-I group gained 12±1% daily. Rats treated with low and medium dose AmpB gained 8±0.5% daily. Rats treated with high dose AmpB lost 10±2% of their body weight daily. Rats treated with IGF-I and AmpB gained 8±2% daily. The urine SG in control groups ranged from 1.020-1.025. The urine specific gravities on day five were as followed: 5 mg/kg 1.015-1.020; 10mg/kg 1.010; 15mg/kg 1.001-1.003. Following sacrifice, AP renal cells were detected microscopically by in situ end labeling of DNA fragmentation(TUNEL). No AP was seen following treatment with D5W and IGF-I. AmpB(5mg/kg) induced few AP cells in the proximal and distal tubule. AmpB (10 mg/kg) induced significant AP in the proximal and distal tubule, in the vas afferens and efferens and the mesangium. AmpB (15 mg/kg) caused pronounced AP in all areas of the kidney. IGF-I prevented renal AP in rats treated with 5 and 10 mg/kg AmpB and significantly reduced the AP in rats treated with 15mg/kg AmpB. AmpB caused a dose-dependent loss of urinary concentrating ability. IGF-I preserved urinary concentrating ability in AmpB treated rats at 1.015-1.020. We conclude that AmpB induces AP in renal cells in vivo in a dose-dependent fashion. It causes loss of weight and urinary concentrating ability in a dose dependent fashion. IGF-I prevents AmpB-induced AP in vivo. It prevents weight loss and preserves urinary concentrating ability.
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(Spon by: Richard N. Fine)(Funded by the Department of Pediatrics, SUNY at Stony Brook; IGF-I was kindly provided by Genentech, Inc).
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Varlam, D., Siddiq, M., Kaskel, F. et al. Insulin-like Growth Factor I (IGF-I) Prevents Amphotericin B (AmpB)-Induced Apoptosis (AP) in the Rat Kidney † 1848. Pediatr Res 43 (Suppl 4), 315 (1998). https://doi.org/10.1203/00006450-199804001-01871
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DOI: https://doi.org/10.1203/00006450-199804001-01871