Selenite Interacting with Thiols Catalytically Releases NO from GSNO, Cleaves Plasmid DNA and Reduces the Hypotensive Effect of GSNO in Rats

Selenium (Se), an essential trace element, plays a significant role in human health. This study aimed to explain the biological effects of selenite (SeO32−) and selenomethionine (SeMet), two Se forms commonly used as dietary supplements, in processes involving nitric oxide (NO) release. We found that products formed by the interaction of SeO32− or SeMet with excess glutathione (GSH), cysteine or homocysteine, catalytically release NO from S-nitrosoglutathione (GSNO) in vitro at physiologically relevant SeO32−concentrations observed in blood. Administration of GSNO into the jugular vein of hypertensive rats decreased systolic and diastolic blood pressure (BP), heart rate, and augmentation index. However, these effects were markedly attenuated when GSNO was pre-incubation with the GSH/SeO32− mixture prior to administration. Furthermore, SeO32− combined with cysteine, homocysteine, GSH and N-acetylcysteine did not induce plasmid DNA (pDNA) cleavage in vitro. However, the presence of GSNO in the SeO32−/thiol mixture caused pDNA cleavage in a bell-shaped manner depending on GSNO concentration. We suggest that under suitable biological conditions thiol/Se-derivatives release NO from NO-donors, but part of the released NO subsequently interacts with the interaction products, resulting in decreased NO bioavaibility in situ. These thiol/SeO32– interactions with NO-donors affect NO-dependent vascular activity and DNA stability. In conclusion, the observed effects may explain selenium’s dual roles in cardiovascular regulation and cancer prevention.