PMID: 7517170Apr 1, 1994Paper

Toxicity of ifosfamide, cyclophosphamide and their metabolites in renal tubular cells in culture

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
M MohrmannM Brandis

Abstract

Ifosfamide (IF) and cyclophosphamide (CP) are highly effective alkylating cytostatic drugs. IF and CP have to be activated through a metabolic step in vivo; numerous metabolites are known. While both IF and its structural isomer CP have severe urotoxic side effects, only IF is also a nephrotoxic drug, causing tubular damage resulting in Fanconi syndrome in some cases. Little information is available regarding the pathogenic mechanism of tubular damage by IF. We used the renal epithelial cell line LLC-PK1, which has many properties of the proximal tubule, in order to investigate the toxicity of IF and CP and of their reactive metabolites 4-hydroxy-IF (4-OH-IF), 4-hydroxy-CP (4-OH-CP), acrolein and chloroacetaldehyde (CAA). Protein content of monolayers, DNA and RNA synthesis were determined by standard techniques (thymidine and uridine incorporation). IF and CP had the lowest toxicities of all compounds tested. Both drugs inhibited thymidine incorporation by about 30% at a concentration of 300 mumol/l after 1 h incubation. 4-OH-IF and 4-OH-CP were significantly more toxic than the parent drugs. Thymidine incorporation, the most sensitive parameter, was reduced by about 70% by 300 mumol/l of either compound. In addition, 4-OH-CP ...Continue Reading

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Citations

Aug 1, 1994·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·M MohrmannM Brandis
Dec 29, 2004·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Stephen D MarksMichael J Dillon
Jun 1, 1998·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C L BroadheadN L Simmons
Dec 22, 2004·Kidney International·Sangeeta R HingoraniGeorge B McDonald
Oct 5, 2013·Journal of Artificial Organs : the Official Journal of the Japanese Society for Artificial Organs·Hiroaki NishimuraMasayuki Nakagawa
Nov 4, 2005·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Gerald SchwerdtMichael Gekle
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