TEMPOL (4-hydroxy-2,2,6,6-TetraMethylPiperidine-1-OxyL) represents a promising compound for the treatment and prevention of numerous diseases and conditions. TEMPOL is a well-known compound investigated by leading researchers at institutions around the world including the National Cancer Institute, Georgetown University, Weizmann Institute, and the Food and Drug Administration. TEMPOL is the focus of more than 2,000 published peer review articles.
TEMPOL is a stable free radical that readily reacts with toxic oxygen species including superoxide (O2.-), hydroxyl radical (.OH), and secondary radicals produced by the oxidation of biological macromolecules, including lipid radicals. TEMPOL reaches every cell in the body and repairs damaged cellular environments thereby increasing mitochondria output and improving overall cellular function. Accordingly, this compound is able to revert the damaged cellular environment that is a common characteristic of all diseases and conditions. In addition, Matrix Biomed has conducted gene array studies on TEMPOL in mice identifying over 500 genes significantly impacted after TEMPOL exposure. TEMPOL increased expression of genes associated with cell viability and overall survival and decreased genes associated with aging and disease.
In the setting of cancer treatment, TEMPOL has the capability to prevent and reduce many of the often life-threatening toxicities associated with chemotherapy and radiation treatment regimens. Chemotherapeutic agents induce oxidative stress indiscriminately in biological systems. Injury to non-targeted tissues often complicates cancer treatment by limiting therapeutic dosages of chemotherapeutic agents and by impairing the quality of life of patients during and after treatment.
TEMPOL has been shown to protect healthy cells from the adverse side effects of chemotherapeutic agents. TEMPOL prevents and reduces oxidative stress thereby preventing corresponding tissue damage (Mitchell 2012). For example, after exposure to a chemotherapeutic agent Doxorubicin, TEMPOL protects the mitochondria against oxidative damage by restoring oxidative balance inside cells (Dickey 2013). Without using TEMPOL as a radioprotector or chemoprotector, both normal cells and cancer cells suffer from severe toxicity. However, TEMPOL exists in a “protective form” and “non-protective form” wherein the TEMPOL molecule exists in its “protective form” in normal oxygenated cells but is rapidly converted to its “non-protective form” in the hypoxic microenvironment of cancer cells. This duality allows cancer treatment regimens to attack cancerous cells while TEMPOL protects the normal cells from the treatment.
This unique mechanism is due to TEMPOL’s cyclic nature. The cyclic nature of TEMPOL is depicted in the figure above. TEMPOL can shuttle between the nitroxyl radical, reduced hydroxylamine, and oxidized oxoammonium cation by way of one- and two-electron-transfer reactions, as seen in the figure above . Reaction 1, in red, is an SOD Mimic that favors an equilibrium towards the nitroxide radical (Krishna et al. 1992, 1996). Reaction 2, in green, is an antioxidant reaction that slightly favors the nitroxide radical (Krishna et al. 1992, 1996). Lastly, reaction 3, in blue, is a reduction reaction that happens very rapidly in the direction of the hydroxylamine (Krishna et al. 1992, 1996). In radiation or chemotherapy, the nitroxide form of TEMPOL (protective form) can protect normal cells from radiation or chemotherapy induced damage but the hydroxylamine form (non-protective form) cannot protect the cancer cells. TEMPOL is the only known compound to possess this functional duality.