Nicotinamide Riboside Protects Brain Development from Drug Toxicity: Preclinical Findings

Synopsis

This study explored the potential neurodevelopmental risks of oseltamivir phosphate (OSE)—a widely used antiviral drug also found in the environment—using zebrafish models. Researchers discovered that OSE exposure, even at medically relevant doses, caused heart abnormalities, hyperactive behavior, social deficits, and impaired learning in developing fish. These effects were linked to neuroinflammation, changes in neurotransmitter levels, and mitochondrial dysfunction, including reduced mitochondrial membrane potential and ATP production. Transcriptomic analysis showed that OSE disrupted oxidative phosphorylation, a key energy process in brain cells. Remarkably, co-treatment with nicotinamide riboside (NR), a vitamin B3–derived NAD+ booster, or acetyl-L-carnitine (ALC), restored mitochondrial function and prevented the behavioral and developmental damage. The findings suggest that OSE overuse may pose neurodevelopmental risks through mitochondrial toxicity and that NR supplementation could help protect brain development from drug-induced mitochondrial damage.

Journal

Science of The Total Environment