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.

In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro

“…We also demonstrated that the nephrotoxic effects of 0.5 mM CAA were prevented by addition to the incubation medium of an equimolar concentration of mesna or a tenfold higher concentration of amifostine [12]. These results were confirmed by several studies conducted by other authors, showing that mesna and amifostine could prevent toxicity of CAA in vitro [30][31][32][33]. Despite the fact that the protecting concentration of thiols compounds were quite different among the various studies (from 200 to 800 μM), it must be emphasised that the protecting effect obtained under in vitro conditions was very efficacious and was promising to also prevent CAA toxicity in clinical practice.…”

Effect of Storing Temperature on Hepatotoxicity and Nephrotoxicity of Ifosfamide in Female Rat

“…The mechanism of such cell death follows the apoptotic cell death (Takahashi et al, 2007), although necrotic mechanism of cell death has also been mentioned by other workers (Daniel et al, 1992). Infiltration of inflammatory leucocytes which already use to accompany necrosis (Schwerdt et al, 2007;Chen et al, 2008) was seen in the present study. The fatty changes or liver steatosis caused by using IFO stored at 10 and 25°C may be related to changes in the chemical structure of the drug due to storing temperature.…”

Neuroprotective effect of mesna (2-mercaptoethane sulfonate) against spinal cord ischemia/reperfusion injury in rabbits

“…3 2-mercaptoethane sulfonate (mesna) is a small, synthetic, highly water-soluble molecule that has the potential to scavenge reactive oxygen species by virtue of its sulfhydryl group. 6 It is principally used to reduce the hemorrhagic cystitis induced by cyclophosphamide and ifosfamide, but it is also widely used as a protective agent against chemotherapy toxicity. To the best of our knowledge, there have been no previous investigations of whether mesna ameliorates neuronal injury and neurotoxicity.…”