Oxidative stress causes lipid peroxidation through an excess of free radicals that damage lipids.
Understanding the Process
Oxidative stress occurs when there's an imbalance between the production of reactive oxygen species (ROS) or free radicals and the body's ability to neutralize them with antioxidants. This imbalance leads to cellular damage. One of the primary targets of this damage is lipids, resulting in lipid peroxidation.
Steps Involved
- Initiation: Free radicals, highly reactive molecules with unpaired electrons, are produced in excess during oxidative stress. These radicals can be generated from various sources, including:
- Normal metabolic processes
- Environmental toxins
- Inflammatory responses
- Radiation exposure
- Propagation: These free radicals attack lipids, particularly polyunsaturated fatty acids (PUFAs) in cell membranes. This attack initiates a chain reaction:
- A free radical abstracts a hydrogen atom from a lipid molecule, creating a lipid radical (L•).
- The lipid radical reacts with oxygen to form a lipid peroxyl radical (LOO•).
- The lipid peroxyl radical can then abstract a hydrogen atom from another lipid molecule, propagating the chain reaction and creating more lipid radicals and lipid hydroperoxides (LOOH).
- Termination: The chain reaction continues until two radicals react to form a non-radical product, or until antioxidants scavenge the free radicals. However, during oxidative stress, this termination process is overwhelmed by the continuous generation of free radicals.
- Amplification: As the reference states, "The oxidative free radicals then cause lipid peroxidation which continues to be unabated leading to generation of more free radicals." This highlights the self-propagating nature of lipid peroxidation.
Consequences of Lipid Peroxidation
Lipid peroxidation has numerous detrimental effects on cells and tissues:
- Membrane Damage: Lipid peroxidation alters the structure and fluidity of cell membranes, disrupting their function and integrity.
- Formation of Toxic Products: Lipid peroxidation generates reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which can modify proteins and DNA, leading to cellular dysfunction and damage.
- Cell Signaling Disruption: The products of lipid peroxidation can act as signaling molecules, contributing to inflammation and other pathological processes.
- Cell Death: Severe lipid peroxidation can lead to cell death through apoptosis or necrosis.
Factors Exacerbating Lipid Peroxidation
Several factors can exacerbate lipid peroxidation during oxidative stress:
- Antioxidant Depletion: Reduced levels of antioxidants like glutathione, vitamin E, and vitamin C hinder the body's ability to quench free radicals. The reference notes that "cellular antioxidant status undergoes severe alteration leaving the cells overexposed to excessive free radicals" during oxidative stress-induced inflammatory diseases.
- Presence of Transition Metals: Metals such as iron and copper can catalyze the decomposition of lipid hydroperoxides, generating more free radicals and accelerating the chain reaction.
- Inflammation: Inflammatory responses can increase the production of ROS and promote lipid peroxidation.
