Topic Overview:
As a near-ubiquitous preservative added to processed foods from hot dogs to bacon as well as a naturally occurring component of green leafy and root vegetables, nitrite has suffered significant negative press due to concerns about its carcinogenic potential when ingested at high levels. Recent research, however, has indicated that this much-maligned molecule may also have potent cytoprotective potential, particularly following ischemia/reperfusion injury to the mammalian heart, liver, and brain.

Dr. Shiva’s research is focused on mitochondrial mechanisms of nitrite-mediated cytoprotection. An intrinsic circulating molecule, nitrite is reduced to bioactive nitric oxide (NO) during ischemia and has been shown to limit apoptosis and cytotoxicity at nanomolar levels in murine models of myocardial, hepatic, and cerebral infarction. Building upon previous studies that have demonstrated NO’s key regulatory role in mitochondrial respiration, Dr. Shiva hypothesized that the cytoprotective effects of nitrite occur at the level of the mitochondrion. In experiments with isolated mitochondria and mice subjected to ischemia/reperfusion, Dr. Shiva demonstrated that treatment with physiological concentrations of nitrite, administered orally or systemically in the mouse, preserved mitrochondrial reperfusion respiration and limited reactive oxygen species-mediated cellular dysfunction. Remarkably, the mitochondria were protected whether nitrite was administered during or 24 hours before the anoxic/reoxygenation event, indicating that nitrite may play a role in a cell-survival program of ischemic preconditioning.

Dr. Shiva’s findings suggest that nitrite modulates mitochondrial resilience to ischemic/reperfusion injury in the heart and liver. As a chemically stable endogenous reservoir of NO with potent therapeutic effects in the nanomolar range, nitrite may well explain the success of the heart-healthy, nitrite-rich Mediterranean diet and spur its further development as a dietary cardioprotective agent.