Lipids play an essential role in both tissue protection and damage. Tissue
ischemia creates anaerobic conditions in which
enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in
membrane lipids, the formation of
aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of
fatty acids that leads to lipotoxicity.
Lipid analysis provides additional insight into the pathogenesis of
ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of
fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of
fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of
fatty acids on cell damage and death. The latter option involves using
PPAR agonists and drugs that modulate the transport of
fatty acids via
carnitine into the interior of the mitochondria or the redirection of long-chain
fatty acids to peroxisomes.