Slow release of oxygen from carbamide peroxide for promoting the proliferation of human brain microvascular endothelial cells under hypoxia

BACKGROUND: Under hypoxic conditions, the brain can undergo irreversible damage. The present study aimed to explore new higher-oxygen-content carbamide peroxide (CP) compounds and the effect of their oxygen-releasing property on human brain microvascular endothelial cell (EC) proliferation under in vitro hypoxic conditions. METHODS: Two different additives including alpha-terpineol and sorbic acid were added to the reaction system to obtain the carbamide peroxide of CP-I and CP-II. RESULTS: We evaluated the oxygen generation capabilities of CP samples by using a portable dissolved oxygen meter. Consequently, alpha-terpineol as a stabilizer exhibited a unique effect on the oxygen generation of CP. CP-I was uniquely able to promote cell proliferation ability at 10 µg·L(−1) for hypoxic conditions, with the proliferation rates being 36.2% compared with the control group. The safety of CP to cells was further verified by calcein-AM/PI staining. Under hypoxic conditions, CP-I at 10 µg·L(−1) promoted the migration rate, and the migration rate being 32.37%. CONCLUSIONS: These compounds have the advantages of simple synthesis, long storage time, low cost, and rich oxygen content. Used spectrophotometry, oxygen electrode test, and indicator titration for testing the oxygen production rate and oxygen production. The results indicate that alpha-terpineol is the best additive. CP-I exhibited the highest oxygen content and a superior effect on the cell phenotype than CP-II, especially under hypoxia. This study is the first to report the effects of CP on cells, and provides new therapeutic insights into cerebrovascular injury repair.