II.

3 Causes Of Damage On Cell Membrane By Free Radicals

Aerobic organisms use molecular oxygen (O2) for respiration or oxidation of nutrients to
obtain energy. Reactive by products of oxygen, such as superoxide anion radical (O2–), hydrogen
peroxide (H2O2), and the highly reactive hydroxyl radicals (·OH), are generated continuously in
cells grown aerobically. Free radicals are produced as the residue of catabolism process in our
body. They are extremely destructive and damage cells if you are exposed to high levels over a
long period of time. They also weaken the immune system, making you vulnerable to diseases
and infections. They can cause damage to your skin, brain, lungs, digestive track, arteries and
your DNA – the genetic code that controls cellular behavior.
In low/moderate concentrations free radicals are involved in normal physiological
functions but excess production of free radicals or decrease in antioxidant level leads to oxidative
stress. It is a harmful process that can be mediates damage to cell structures, including lipids,
proteins, RNA and DNA which leads to number of diseases. A variety of synthetic medicine
employed in the treatment of different diseases also capable to generate free radicals in body
which may causes another disease[1].
There are 2 factors that involves in causing damage in cell membrane, endogenous and
exogenous factor. Endogenous factor is factor which comes from within the organism. Example
of endogenous factors :
1. Inflammation initiates neutrophils and macrophages to produce ROS and RNS
2. In mitochondria-catalyzed electron transport reactions, oxygen free radicals produced as by
product.
3. ROS generated by the metabolism of arachidonic acid, platelets, macrophages and smooth
muscle cells.
On the other hand, exogenous factor is factor which comes from outside the organism.
Exogenous factors include human activities and habits that could also cause damages on cell
membrane because of free radicals. Another factor beside human habits is environmental factor.
These are some free radical substances which are harmful for our cell membrane :
1. Cigarette smoke
Cigarette smoke is operationally divided into gas-phase smoke and particulate matter(or tar).
Tar is the material retained on a filter, whereas gas-phase smoke passes through the filter. The tar
phase contains several relatively stable free radicals; we have identified the principal radical as a
quinine /hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2
polymer is an active redox system that is capable of reducing molecular oxygen to produce
superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals.
The gas phase of cigarette smoke contains small oxygen- and carbon-centered radicals that
are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in
the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then
reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the
meta-stable products derived from these radical reactions may be responsible for the inactivation
of a proteinase inhibitor by fresh smoke.
2. Air pollution
Ambient air contains a range of pollutants, the exact combination of which varies from one
microenvironment to the next. Many of the individual pollutants that make up this ambient mix
are free radicals (for example, nitrogen dioxide) or have the ability to drive free radical reactions
(for example,ozone and particulates). As a consequence, exposure to a wide
range of air pollutants gives rise to oxidative stress within the lung, and this appears to initiate
responses that are particularly dangerous to susceptible members of the population [2]
Ozone is a relatively insoluble gas. It is very reactive, and uptake is directly related to
reactions with substrates present in the lung lining fluid, the first compartment it encounters on
entering the lung. Symptoms include decreased lung function, increased airway hyperreactivity,
and pulmonary inflammation. Those individuals with pre-existing conditions such as asthma and
chronic obstructive pulmonary disease generally experience an exacerbation of their symptoms.
The major source of nitrogen dioxide in urban areas is traffic with ambient concentrations
fluctuating with the morning and evening rush hours. Indoors, cooking with gas appliances and
cigarette smoke are the major sources. Animal studies have shown that high concentrations of
nitrogen dioxide can damage the lung, while cell culture experiments indicate that exposure
increases cell permeability and injury.
3. UV Radiation
It has been suggested that ultraviolet light induces free radical formation in skin, leading
to photoaging and cancer. Direct DNA damage can occur when DNA directly absorbs
the UV-B-photon. UV-B light causes thymine base pairs next to each other in genetic
sequences to bond together into pyrimidine dimmers, a disruption in the strand, which
reproductive enzymes cannot copy. It causes sunburn and it triggers the production
of melanin.
UV induced generation of ROS in the skin develops oxidative stress, when their
formation exceeds the antioxidant defence ability of the target cell. Acute exposure to UVR
depletes the catalase activity in the skin and increases protein oxidation. The primary
mechanism by which UVR initiates molecular responses in human skin is via photochemical
generation of ROS mainly formation of superoxide anion (O2−•), hydrogen peroxide (H2O2),
hydroxyl radical (OH•), and singlet oxygen (O2) . UVR penetrates the skin, reaches the cells,
and is absorbed by DNA, leading to the formation of photoproducts that inactivate the
functions of DNA [3]
4. Pesticides
Pesticides are biocides capable of killing all forms of life. Organophosphates (OP)
pesticides are commonly used worldwide in agricultural and in pest control. It is reported
that OP pesticides, besides there inhibitory effect on AChE ,also changes characteristic of
oxidative stress superoxide dismutase (SOD), whose substrate is free radical (superoxide
anion; O2-) catalyzes dismutation reaction resulting in the generation of hydrogen peroxide.
This H2O2 is decomposed to water and molecular oxygen by the action of catalase .When
the radical production overwhelms the endogenous levels decreased , they cause
considerable cell damage / death[4]
1. S. Sen,Et Al (2010) Free Radicals, Antioxidants, Diseases And Phytomedicines: Current
Status And Future Prospect. International Journal Of Pharmaceutical Sciences Review
And Research. Pg.91
2. F. Kelly (2003) Oxidative Stress: Its Role In Air Pollution And Adverse Health Effects.
Occup Environ Med. Pg 613
3. B. PoljˇSak, Et Al (2012) Free Radicals And Extrinsic Skin Aging. Dermatology
Research And Practice
4. Mishra B.P,Et Al (2013). Antioxidant Status And Oxidative Stress In Organophosphate
Pesticide Poisoning. Iosr Journal Of Dental And Medical Sciences (Iosr-Jdms). Pg 20.