To study the relationship between cisplatin-mediated hair cell death and NAD+ contents, Zhan and colleagues stimulated different NAD+ synthesis pathways. Several compounds were able to increase NAD+ contents in cochlear explants, including the NAD+ precursor NMN. In addition, supplementation of a different intermediate L-Tryptophan and a specific inhibitor (TES-1025) of an enzyme that limits NAD+ synthesis also increased NAD+ levels. However, direct NAD+ supplement to cochlear explants had little effect on intracellular NAD+ level.
In addition to reductions in hair cell number, cisplatin treatment caused noticeable defects in the hearing abilities of mice. But in mice administered cisplatin, NMN treatment led to smaller hearing threshold shifts, which are indicative of increased hearing sensitivity, compared with the group that didn’t receive NMN.