title: Mesna or cysteine prevents chloroacetaldehyde-induced cell death of human proximal tubule cells.
abstract: Chloroacetaldehyde (CAA) is formed in the body from the chemotherapeutically used drug ifosfamide (IFO). CAA leads to cell death in proximal tubule cells mainly through the mechanism of necrosis rather than apoptosis. During chemotherapy, 2-mercaptosulfonic acid (mesna) is used with IFO to protect the urothel from cell damage. Little is known of the effect of mesna on renal proximal tubule cells, the primary site of damage after IFO treatment. Mesna contains a sulfhydryl (SH) group. To clarify whether SH-group-containing molecules can prevent CAA-induced cell death, we studied the effect of mesna and cysteine on necrosis, apoptosis, and protein content in a human proximal tubule-derived cell line (IHKE cells) treated with CAA. Both substances prevented CAA-induced necrotic cell death and protein loss and restored CAA-inhibited caspase-3 activity. CAA also prevented cisplatin-induced apoptosis. This inhibition was reversible in the presence of glutathione (GSH). We conclude that SH-containing molecules can protect proximal tubule cells from cell death because they interact with CAA before CAA can disturb other important cellular SH groups. A sufficient supply of intra- and extracellular SH groups during IFO chemotherapy may therefore have the ability to protect renal tubule cells from cell death.
authors.affiliation: Department of Physiology, University of Würzburg, Würzburg, Germany. gerald.schwerdt@mail.uni-wuerzburg.de
authors.forename: Gerald
authors.initials: G
authors.lastname: Schwerdt
authors.forename: Antje
authors.initials: A
authors.lastname: Kirchhoff
authors.forename: Ruth
authors.initials: R
authors.lastname: Freudinger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wollny
authors.forename: Andreas
authors.initials: A
authors.lastname: Benesic
authors.forename: Michael
authors.initials: M
authors.lastname: Gekle
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003545:Cysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D015080:Mesna / Q000494:pharmacology*; D009336:Necrosis / Q000139:chemically induced; D020011:Protective Agents / Q000494:pharmacology*
chemical_list: D020011:Protective Agents; C004656:chloroacetaldehyde; D005978:Glutathione; D000079:Acetaldehyde; D003545:Cysteine; D015080:Mesna