Nicotinamide Alleviates Synergistic Impairment of Intestinal Barrier Caused by MC-LR and NaNO₂ Coexposure

Microcystin-LR (MC-LR) and nitrites from the environment and daily life can be ingested and absorbed by humans via the digestive tract. However, their combined effects on intestinal health remain unclear. Here, the combined impact of MC-LR and sodium nitrite (NaNO₂) on the intestines of mice was investigated under actual human exposure conditions. After mice were exposed to MC-LR (10, 100 μg/L) and NaNO₂ (30, 300 mg/L) individual and in combination for 6 months, it was found that MC-LR and NaNO₂ synergistically decreased intestinal permeability and disrupted intestinal physical, chemical, immune, and microbial barriers. In the coexposure groups, the synergistic impairment to the intestinal barrier was noted with increasing concentrations of MC-LR or NaNO₂, but this adverse effect was alleviated by nicotinamide supplementation. This study underscores the potential risks of simultaneous ingestion of MC-LR and nitrite on intestinal health. The protective role of nicotinamide suggests avenues for therapeutic intervention against environmental toxin-induced intestinal impairment.