Nicotinamide Riboside Prevents Chemotherapy-Induced Peripheral Neuropathy: Preclinical Findings

Synopsis

Paclitaxel (PTX) is a widely used chemotherapy drug for cancers such as breast, lung, and ovarian cancer, but one of its major side effects is chemotherapy-induced peripheral neuropathy (CIPN)—nerve damage that causes pain, numbness, and reduced quality of life. This study discovered that activating SIRT3, a mitochondrial NAD+-dependent enzyme that regulates energy metabolism and antioxidant defenses, helps prevent this nerve damage. Treatment with nicotinamide riboside (NR), a vitamin B3–derived NAD+ precursor, restored SIRT3 activity and protected dorsal root ganglion (DRG) neurons from oxidative stress caused by paclitaxel. NR did this by activating the SIRT3–MnSOD2 and SIRT3–Nrf2 pathways, which enhance mitochondrial function and reduce oxidative injury. Remarkably, NR not only protected nerves but also enhanced paclitaxel’s anticancer effects. These findings suggest that NR supplementation could be a promising strategy to prevent or treat paclitaxel-induced neuropathy while maintaining or improving cancer treatment outcomes.

Journal

Toxicology and Applied Pharmacology