Oxidative stress

Introduction

Oxidative stress is a state of imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants. This imbalance leads to damage to cells, proteins, and DNA, which can contribute to aging and a variety of diseases.

Biochemical Basis

The biochemical basis of oxidative stress involves the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These are chemically reactive molecules containing oxygen and nitrogen, respectively. They are created by several endogenous and exogenous processes. Endogenous sources include the mitochondrial electron transport chain, peroxisomes, inflammation, phagocytosis, arachidonate pathways, and ischemia. Exogenous sources include exposure to radiation, pollution, certain drugs, industrial solvents, and cigarette smoke.

A close-up view of a mitochondrion, the primary site of ROS production in cells.

ROS and RNS play a dual role in biological systems, as they can be either harmful or beneficial to living systems. At low or moderate concentrations, ROS and RNS can be beneficial, playing a role in cell signaling systems and the defense against infectious agents. However, at high concentrations, they generate oxidative stress, a damaging process that can alter the cell’s lipids, proteins, and DNA, leading to a variety of pathophysiological conditions.

Role in Disease

Oxidative stress is implicated in many diseases, including cancer, neurodegenerative diseases like Parkinson's disease and Alzheimer's disease, cardiovascular diseases, diabetes, rheumatoid arthritis, chronic inflammation, stroke, and sepsis. It is also involved in conditions such as aging, male infertility, and pregnancy complications.

In cancer, oxidative stress can cause DNA damage, leading to mutations that contribute to the development and progression of the disease. In neurodegenerative diseases, oxidative stress can lead to neuronal damage and death, contributing to the symptoms and progression of these disorders.

In cardiovascular diseases, oxidative stress can contribute to atherosclerosis, heart failure, myocardial infarction, and cardiac hypertrophy. In diabetes, oxidative stress can lead to insulin resistance and the death of pancreatic beta cells, which produce insulin.

Oxidative Stress and Aging

Oxidative stress is also thought to play a role in the aging process. The free radical theory of aging, proposed by Denham Harman in the 1950s, suggests that the accumulation of damage caused by ROS and RNS over time leads to the physiological changes associated with aging.

While this theory has been influential, it is not without controversy. Some studies have found that increasing antioxidant levels in animals does not necessarily increase lifespan, suggesting that oxidative stress may not be the only factor contributing to aging. However, other research has found that reducing oxidative stress can extend lifespan in certain organisms, suggesting that it does play a significant role.

Measurement and Detection

The measurement and detection of oxidative stress can be challenging due to the instability and reactivity of ROS and RNS. However, several methods have been developed to measure these species and the damage they cause.

One common method is the measurement of malondialdehyde (MDA), a product of lipid peroxidation, which can be detected in the blood. Other methods include the measurement of protein carbonyls, a marker of protein oxidation, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidation.

Management and Treatment

The management and treatment of oxidative stress typically involve the use of antioxidants, which can neutralize ROS and RNS. These can include dietary antioxidants, such as vitamins C and E, as well as endogenous antioxidants, such as glutathione.

In addition to antioxidant therapy, other strategies for managing oxidative stress can include lifestyle changes, such as regular exercise and a healthy diet, as well as the avoidance of exogenous sources of ROS and RNS, such as smoking and exposure to pollution.