Image from NIDCD
Cisplatin (green) in the stria vascularis of a mouse inner ear.
Researchers have gained new insight into hearing loss caused by cisplatin.
By measuring and mapping cisplatin retention in mouse and human inner ear tissues, the researchers found that cisplatin builds up in the inner ear and can remain there for years.
The team also found that a region in the inner ear called the stria vascularis could be targeted to prevent hearing loss resulting from cisplatin.
Lisa L. Cunningham, PhD, of the National Institute on Deafness and other Communications Disorders (NIDCD) in Bethesda, Maryland, and her colleagues reported these findings in Nature Communications.
The researchers noted that cisplatin can cause permanent hearing loss in 40% to 80% of treated patients. The team’s new findings help explain why.
The researchers found that, in most areas of the body, cisplatin is eliminated within days or weeks of treatment, but, in the inner ear, the drug remains much longer.
The team developed a mouse model that represents cisplatin-induced hearing loss seen in human patients.
By looking at inner ear tissue of mice after the first, second, and third cisplatin treatment, the researchers saw that cisplatin remained in the mouse inner ear much longer than in most other body tissues, and the drug builds up with each successive treatment.
The team also studied inner ear tissue donated by deceased adults who had been treated with cisplatin and found the drug is retained in the inner ear months or years after treatment.
When the researchers examined inner ear tissue from a child, they found cisplatin buildup that was even higher than that seen in adults.
Taken together, these results suggest the inner ear readily takes up cisplatin but has limited ability to remove the drug.
In mice and human tissues, the researchers saw the highest buildup of cisplatin in a part of the inner ear called the stria vascularis, which helps maintain the positive electrical charge in inner ear fluid that certain cells need to detect sound.
The team found the accumulation of cisplatin in the stria vascularis contributed to cisplatin-related hearing loss.
“Our findings suggest that if we can prevent cisplatin from entering the stria vascularis in the inner ear during treatment, we may be able to protect cancer patients from developing cisplatin-induced hearing loss,” Dr Cunningham said.
