PMID: 7542792May 1, 1995Paper

Ifosfamide and mesna: effects on the Na/H exchanger activity in renal epithelial cells in culture (LLC-PK1)

Renal Physiology and Biochemistry
M MohrmannM Brandis

Abstract

Ifosfamide (IF) is an alkylating cytostatic with urotoxic and tubulotoxic side effects which may result in the development of Fanconi syndrome in children. While the urotoxicity of IF is effectively prevented by the uroprotective thiol compound sodium-2-mercaptoethanesulfonate (Mesna), tubulo-toxicity of IF may occur even in the presence of Mesna and in the absence of any signs of urotoxicity. Using the renal tubular cell line LLC-PK1, we investigated whether there is a protective effect of Mesna or of its major dimeric metabolite Dimesna against metabolites of IF with respect to the Na/H exchanger activity. We tested the major IF metabolites 4-hydroperoxy-IF (4-OOH-IF), chloroacetaldehyde (CAA), and acrolein. All metabolites significantly inhibit the Na/H exchanger activity. Half-maximal inhibition of transport occurs at concentrations of 120 mumol/l (4-OOH-IF), 80 (CAA), and 60 mumol/l (acrolein) after 2 h of incubation. The onset of the inhibitory effect of all three metabolites is rapid. Complete inhibition of Na/H exchange by acrolein and CAA is present after a 6-hour exposure to 100 mumol/l of the respective metabolite, while 100 mumol/l 4-OOH-IF causes only 50% inhibition after 24 h of incubation. Dimesna, which the prox...Continue Reading

Citations

Jan 25, 2008·Archives of Toxicology·Zeinab YaseenLaurence Dubourg
Oct 31, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·James Springate, Mary Taub
Jul 10, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Emad L ZakiMary Taub
Jun 1, 1998·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C L BroadheadN L Simmons
Sep 7, 1999·In Vitro Cellular & Developmental Biology. Animal·J SpringateM Taub

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