EC Pharmacology and Toxicology

Now a day, many scientists working on aging, are focusing on polysulfide metabolism and sulfur respiration research in coordination with anti-aging phenotypes. Several studies suggests that sulfur respiration is good for health with specific emphasis on healthy aging as polysulfide or hydropersulfide species are activating the autophagy pathway, and also possessing anti-inflammatory activity, regulation of mitochondrial metabolism and so on. Recent studies also suggest hydropersulfide as a super radical scavenger, but the precise molecular mechanism has yet to be unveiled. Very recent finding of Barayeu U. et al. suggested that hydropersulfide has auto-recycling capacity and after generating recycled hydropersulfide, it becomes inert/inactive until it gets favorable reaction environment in the next. Under these circumstance, very minute amount of exogenous supplementation of sulfane sulfur molecule can activate the hydropresulfide-mediated radical scavenging by utilizing the inert hydropersulfide or recycled hydropersulfide that works a as super radical scavenger than some other radical scavenger, such as N-acetyl cysteine (NAC). Barayeu U., et al. also suggested that by this alternative function, hydropersulfide also bypasses the ferroptosis-mediated cell death and support cellular longevity that could be a deteriorating approach for cancer metastasis. This study also gives a clue about how stressed tumor cells escape cellular death.

Keywords: Hydropersulfide; Ferroptosis; Radical Scavenger; Longevity; Cancer

1. Alam MM. “Essence of antioxidants in aging science: NRF2 a true fact”. CPQ Medicine 5 (2019): 1-5.
2. Alam MM., et al. “Glucocorticoid receptor signaling represses the antioxidant response by inhibiting histone acetylation mediated by the transcriptional activator NRF2”. Journal of Biological Chemistry 18 (2017): 7519-7530.
3. Goto M., et al. “Alcohol dehydrogenase 3 contributes to the protection of liver from nonalcoholic steatohepatitis”. Genes to Cells 20 (2015): 464-480.
4. Yamamoto M., et al. “The KEAP1-NRF2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis”. Physiological Reviews 98 (2018): 1169-1203.
5. Motohashi H., et al. “Sulfur-utilizing cytoprotection and energy metabolism”. Current Opinion in Physiology 9 (2019): 1-8.
6. Alam MM., et al. “Contribution of NRF2 to sulfur metabolism and mitochondrial activity”. Redox Biology (2023): 102624.
7. Akaike T., et al. “Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics”. Nature Communications 8 (2017): 1177.
8. Stockwell BR., et al. “Emerging mechanisms and disease relevance of ferroptosis”. Trends in Cell Biology 6 (2020): 478-490.
9. Barayeu U., et al. “Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals”. Nature Chemical Biology 19 (2023): 28-37.