Researchers Learn Why Some Platinum Drugs Are Toxic to Ear..

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Researchers Learn Why Some Platinum Drugs Are Toxic to Ear Tissue

Ototoxicity, or damage to inner-ear cells that detect sound, is a known side effect of platinum-based chemotherapy drugs. The damage is much more common with cisplatin than with oxaliplatin, though the reason for this difference has been unknown. Swedish researchers have now tested some of the possible explanations by comparing the activity of these two drugs in the inner ears of guinea pigs. Their analysis appeared December 30 in the Journal of the National Cancer Institute.

Cisplatin and oxaliplatin are thought to work by attaching to DNA and binding the genetic material so that it cannot replicate properly, thereby preventing cell division. But because the cells in the inner ear are already differentiated and less susceptible to this mechanism, the researchers hypothesized that cisplatin and oxaliplatin may also have an effect outside of the nucleus by generating reactive oxygen species, or free radicals.

They cultured colon carcinoma cells and measured the extent to which each drug induced cell death, or apoptosis, and found that cisplatin is significantly more dependent on free radicals than is oxaliplatin for triggering death in these cells. Guinea pigs showed more signs of free radical-induced apoptosis in their cochlea after exposure to cisplatin than to oxaliplatin.

The two drugs also showed marked effects on the transmission of sound signals from the cochlea to the brain, with cisplatin causing more damage to the hair cells that detect vibrations, and ultimately causing deafness, while comparable exposure to oxaliplatin did not. Cisplatin absorbed into the inner ear more easily than oxaliplatin did, and it remained in the tissues for a longer time.

“[it] should not be taken for granted that human subjects have the same cochlear pharmacokinetics [as guinea pigs],” the researchers noted, though they believe that the major aspects of their conclusions are valid for humans.