Fig. 3

Mechanism of lipid peroxidation. Lipid peroxidation occurs in three steps: 1-initiation, 2-propagation, and 3-termination. 1- Initiation: the vicious cycle of lipid peroxidation starts with a radical attack (X●) which reacts with polyunsaturated fatty acids (PUFA) in cell membrane phospholipids (PL) and removes their bis-allylic hydrogen, transforming PUFA into a lipid/ alkyl radical (PL-PUFA●). 2- Propagation: Once a lipid radical is formed, a chain reaction of lipid radical formation continues. Molecular oxygen (O2) reacts with the formed PL-PUFA●, producing a lipid peroxyl radical (PL-PUFAOO●) which interacts with another membrane PL-PUFA, removes its bis-allylic hydrogen to form a lipid hydroperoxide radical (PL-PUFA-OOH●) and another PL-PUFA● that propagates the cycle. 2\- Amplification: iron feeds this chain reaction through a Fenton-like reaction. Ferrous iron (Fe+2) reacts with PL-PUFA-OOH●, gets oxidized to Fe+3, and forms a hydroxide anion and a highly reactive alkoxyl (PL-PUFA-O●) radical that causes an exponential increase in lipid radical formation. 3- Termination: the cycle can be ended either by the presence of an antioxidant that turns radicals into non-radicals or by the interaction of two radicals, forming O2 and a non-radical