Diallyl trisulfide , also known as Allitridin, is an organosulfur compound with the formula S2. It is one of several produced by the hydrolysis of allicin, including diallyl disulfide and diallyl tetrasulfide, DATS is one of the most potent.
Biological applications
Many health benefits of garlic are attributed in part to DATS. These benefits include anti-cancer effects, platelet aggregation, blood pressure reduction, decreases in cholesterol levels, and increases in levels of reactive oxygen species. DATS has been shown to selectively kill cancerous cells in the prostate and breast, leaving healthy cells unharmed. This effect is attributed to increased reactive oxygen species within cancer cells, increased the number of cells that arrest in the G2 phase of mitosis, and promote an increase in caspase-3 activity. These effects appear to contribute to the apoptosis of cancer cells and a decrease in cancer cellproliferation. DATS can be metabolized by glutathione in red blood cells to form hydrogen sulfide. This conversion occurs at a consistent rate over a prolonged period of time, rendering DATS a good source of H2S. H2S is a cardioprotective agent that has antioxidant, anti-inflammatory, and anti-apoptotic effects,. A major topic of research is the impact of hydrogen sulfide on reducing myocardial ischemia-reperfusion injury. Reperfusion injury is a significant threat to myocardial function that arises with the reintroduction of blood flow to the heart following an ischemic episode. Reperfusion triggers an inflammatory response and often results in oxidative damage. H2S decreases injury through many different effects such a decrease in oxidative stress, maintenance of mitochondrial function, and increased eNOS activation. eNOS is activated via phosphorylation by H2S through the activation of the PI3K/Akt pathway, which increases the formation and bioavailability of nitric oxide. This negatively impacts mitochondria functionality. The mitochondria has been known to protect the heart from ischemic-reperfusion injury through the opening of the ATP-sensitive K+ channel,. This causes vasodilation and improves hemodynamics. DATS is a promising treatment for cardiac arrhythmias through its ability to change the opening of the human ether-à-go-go-related channel. hERG is the pore-forming subunit of potassium channels that create delayed rectifier potassium ion currents in many cells, including cardiac myocytes. The delayed rectifier potassium ion current is largely responsible for the repolarization of ventricular cardiac myocytes by permitting potassium efflux. DATS causes a decrease in the steady-state inactivation, alters deactivation, and impairs trafficking of the hERG channel from the endoplasmic reticulum to the plasma membrane of the cell. This decreases the amount of functional potassium ion rectifier channels on the cell membrane and thus, slows depolarization. However, hERG trafficking impairment has also been shown to cause arrhythmias due to the development of long QT syndrome and should be considered in drug development.
