Selenium-containing peptides as effective alleviators for low-level lead induced neural damage

The TSeMMM and SeMDPGQQ, two selenium-containing peptides derived from Se-enriched rice protein hydrolysates, have previously been demonstrated to show neuroprotective properties against high-dose lead exposure. However, the potential toxicological effects of these functional peptides on low-dose lead-induced neurotoxicity remain poorly understood. The present study aimed to investigate the protective mechanism of two selenium-containing peptides in mitigating low-dose Pb 2+ -induced damage in HT22 cells. Results showed that treatment with 40 μmol/L Pb 2+ significantly reduced cell viability and increased apoptosis, both of which were alleviated by 40 μmol/L TSeMMM and SeMDPGQQ treatment. Furthermore, two peptides exhibited antioxidant potentials by reducing reactive oxygen species levels to 32.19% and 79.29% of the model group, respectively. They also enhanced antioxidant enzyme activities and mitigated oxidative stress through activation of the Keap1/Nrf2 pathway. Additionally, two peptides improved mitochondrial function by elevating mitochondrial membrane potential, ATP production while dramatically reducing reactive oxygen species levels. Interestingly, TSeMMM exhibited superior neurointerventional effects compared to SeMDPGQQ. The RNA sequencing analysis revealed that TSeMMM modulated gene expressions related to oxidative stress and neuroprotective function. The study provides insights into the protective mechanism underlying selenium-containing peptides for mitigating neuronal damage.