Vol.3, No.1, 32-41 (2013) Open Journal of Preventive Medicine
http://dx.doi.org/10.4236/ojpm.2013.31005
Broad overview of oxidative stress and its
complications in human health
Peter Kovacic1*, Ratnasamy Somanathan1,2
1Department of Chemistry and Biochemistry, San Diego State University, San Diego, USA;
*Corresponding Author:
2Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Tijuana, Mexico
Received 2 November 2012; revised 5 December 2012; accepted 14 December 2012
ABSTRACT
There is extensive literature dealing with toxicity
and human health. A goodly portion puts focus
on involvement of electron transfer, reactive
oxygen species and oxidative stress involving
body organs. Th ere is evidence for pr evention or
amelioration by antioxidants. This is one mecha-
nism which is part of a multifaceted mode of
action. This review comprises an update of ear-
lier literature.
Keywords: Health; Organ Toxicity; Oxidative Stress;
Reactive Oxygen Species; Electron Transfer
1. INTRODUCTION
Abundant literature exists on involvement of reactive
oxygen species (ROS) and oxidative stress (OS) on hu-
man health. Various reviews (see main text) in the past
have addressed the topic in relation to organ toxicity.
The present review provides a literature update including
the following organs: lungs, skin, kidney, heart, repro-
ductive and mitochondria. The preponderance of bioac-
tive substances or their metabolites incorporate electron
transfer (ET) functionalities, which, we believe, play an
important role in physiological responses. These main
groups include quinones (or phenolic precursors), metal
complexes (or complexors), aromatic nitro compounds
(or reduced hydroxylamine and nitroso derivatives), and
conjugated imines (or iminium species). In vivo redox
cycling with oxygen can occur giving rise to OS through
generation of ROS (Scheme 1), such as hydrogen perox-
ide, hydroperoxides, alkyl peroxides, and diverse radicals
(hydroxyl, alkoxyl, hydroperoxyl, and superoxide). In
some cases, ET results in interference with normal elec-
trical effects, e.g., in respiration or neurochemistry. Gen-
erally, active entities possessing ET groups display re-
duction potentials in the physiologically responsive
range, i. e., more positive than −0.5 V. ET, ROS, and OS
have been increasingly implicated in the mode of action
of drugs and toxins (toxicants), e.g. anti-infective agents
[1], anticancer drugs [2,3], carcinogens [4], and toxins
[5].
There is a plethora of experimental evidence sup-
porting the theoretical framework, including generation
of the common ROS, lipid peroxidation, degeneration
products of oxidation, depletion of AOs, effect of ex-
ogenous AOs, DNA oxidation and cleavage products, as
well as electrochemical data. This comprehensive, uni-
fying mechanism is in keeping with the frequent obser-
vations that many ET substances display a variety of
activities, e.g., multiple drug properties, as well as toxic
effects.
Diverse mechanisms have been proposed for these
agents. However, there has not been recognition for a
unifying theme involving ET-ROS-OS. The unifying
relationships lend credence to the proposed involvement
of ET-ROS-OS in the physiological effects addressed in
this review, and comprise an extension of the prior me-
chanistic framework. However, it should be empha-
sized that physiological activity is often complex and
multifaceted, with various modes of action involved. A
number of original references may be found in the re-
views and articles cited; in many cases, references are
representative.
ET Agent(ETAgent)
O2
-ET Agent
O2
e
,2H
+
HOOH HO
Fe2+
e
Scheme 1. Formation of ROS and RNS. Shown is ET resulting in formation of superoxide which serves as precursor of other
ROS.

P. Kovacic, R. Somanathan / Open Journal of Preventive Medicine 3 (2013) 32-41 33
2. DISCUSSION
2.1. Neurodegenerative Diseases
There has been treatment of neurotoxicity and neu-
rodegenerative diseases involving ROS and OS. A re-
cent review represents an update of neurodegenerative
diseases based on extensive literature [6]. The redox ap-
proach comprises a unifying theme which can be applied
to a large number of illnesses in this class, including
Parkinson’s, Huntington’s, Alzheimer’s, prions, Down’s
syndrome, ataxia, multiple sclerosis, Creutzfeldt-Jacob
disease, amyotrophic lateral sclerosis, schizophrenia, and
tardive dyskinesia. An earlier review addressed neuro-
degeneration from a similar mechanistic viewpoint based
on ROS-OS [7].
The brain consumes more oxygen under physiological
conditions than other organs, thereby increasing its sus-
ceptibility to OS since generation of higher levels of
ROS can lead to pathological changes when these are in
excess of the buffering capacity of endogenous antioxi-
dant systems [8]. Extensive data on OS, signaling path-
ways, cell death and neuroprotection have been gener-
ated in many studies.
Hyperoxia produces toxicity, including that of the
nervous system. The mammalian brain appears to be
particularly sensitive to oxidative damage, one reason
being the high oxygen consumption. Rises in calcium
interfere with mitochondrial function (including neural),
increasing formation of superoxide which can react with
nitric oxide (NO) to form the potent oxidant peroxyni-
trite (ONOO-), accompanied by lipid peroxidation. Sev-
eral neurotransmitters, including dopamine, L-DOPA,
serotonin and norepinephrine, can produce ROS, evi-
dently via quinone/semiquinone metabolites. Iron is
found throughout the brain as complexes with various
proteins (see Role of Iron below). Neural membrane lip-
ids are replete with polyunsaturated fatty acids whose
oxidation products, such as 4-hydroxynonenal and 4-
oxononenal [9], can act as sources of ROS, and are espe-
cially cytotoxic to neurons. Brain metabolism generates
an abundance of hydrogen peroxide via SODs (superox-
ide dismutases) and other enzymes [7]. AO defenses are
modest, such as catalase levels. Brain microglia can be-
come activated to produce superoxide, hydrogen per-
oxide and cytokines. Microglia and astrocytes are major
players in brain inflammation which is associated with
ROS [10]. Some cytochromes leak electrons during the
catalytic redox cycle, thus providing ROS [7]. An- other
source of brain ROS is NADPH oxidase enzymes. He-
moglobin, a neurotoxin, can release heme which is a
powerful promoter of lipid peroxidation. The complex of
hemoglobin with NO can also generate OS [11]. The
Halliwell review presents various means for defense
against neurotoxins [7]. There is also reference to earlier
treatment of neurodegenerative diseases.
A broad overview of neurotoxins was presented based
on electron transfer (ET), reactive oxygen species (ROS),
and oxidative stress (OS) [12]. It is relevant that metabo-
lites from toxins generally posses ET functionalities
which can participate in redox cycling. Toxic effects at
the molecular level include lipid peroxidation, DNA at-
tack, adduction, enzyme inhibition, oxidative attack on
the CNS, and cell signaling. The toxins fall into many
categories. Beneficial effects of AOs are documented. A
related update was reported in 2012 [13]. A similar arti-
cle deals with nitric oxide (NO), catecholamine and glu-
tamate [14]. The review treats the mechanism of these
agents as important neurotransmitters and as neurotoxins,
based on involvement of ET-ROS-OS.
Role of Iron
A recent review presents a unifying theme for cellular
death and neurotoxicity by iron agents [6,15]. The basic
theme involves continuing and autocatalytic generation
of hydroxyl radicals by way of the Fenton reaction in-
volving poorly liganded iron.
3. PULMONARY TOXICITY
The pulmonary system is one of the main targets for
toxicity. In the industrial age, there has been a large in-
crease in atmospheric pollutants. Many adverse reactions
can occur, some of the principal ones being asthma,
COPD and cancer.
It is often unclear what role natural components play
in the mechanism of pathogenesis. However, a common
factor appears to be the upregulation of ROS in lung
cells upon exposure. In vivo redox cycling with oxygen
can occur giving rise to OS through generation of ROS.
ROS can arise from diverse sources, both endogenous
and exogenous [16]. Reduction of O2 to ROS, e.g., su-
peroxide, occurs as a by-product of metabolism. When
cellular injury occurs, release of species, such as iron,
into extracellular space can lead to generation of delete-
rious ROS. Neutrophils and macrophages are adept at
transforming oxygen into ROS which eliminate foreign
organisms, accompanied by the undesirable effect of OS
on normal cells. The lung is especially susceptible to
injury by this gas. For example, hyperoxia damages en-
dothelial and alveolar epithelial cells [17]. A recent re-
view deals with the consequence of hyperoxia and toxic-
ity of oxygen in the lung [18]. Exposure results in in-
creased intracellular generation of superoxide and, hence,
of other ROS, with ensuing autoxidation reactions.
A dramatic example of lung toxicity involving ROS is
adult respiratory distress syndrome (ARDS) which is
brought about by trauma, shock, sepsis, vomiting, and
inhalation of toxins. Inflammation, a common result of

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34
lung insult by toxic substances, is a precursor of subse-
quent events triggered by ROS. There is considerable
evidence that OS is a contributing factor in ARDS [17].
We wish to emphasize the following quote: “In general,
free radicals represent an important component in the
pathogenesis of lung disease” [16]. The role of ROS in
lung damage is further buttressed by the increased ac-
tiveity of free radical-scavenging enzymes in lungs chal-
lenged by a variety of toxins.
There is appreciable literature on ROS, OS and pul-
monary toxicity. In our 2009 review, we surveyed a
number of pulmonary toxicants [16]. In this review only
those toxicants from more recent years will be cited.
3.1. Role of Nanomaterials
In recent years, a wide range of nanomaterials have
been developed for various applications. Increasing evi-
dence suggests that the special physicochemical proper-
ties of these nanomaterials pose potential risk to human
health. Recent reviews in this area deal with the biome-
chanism and toxicity of nanoparticles, including pulmo-
nary insults [19,20].
Data indicate that the composition and size of nano-
materials, as well as the target cell type, are critical de-
terminants of intracellular responses, degree of cytotox-
icity and potential mechanism of toxicity [21]. ROS
plays a major role in its toxicity. Alveolar epithelial cells
exposed to manganese (II,III)oxide nanoparticles gener-
ated ROS leading to OS and apoptosis [22]. Copper ox-
ide nanoparticles induce OS and cytotoxicity in airway
epithelial cells [23].
A study correlated the conduction band energy with
cellular redox potential of Co3O4, Cr2O3, Ni2O3, Mn2O3
and CoO nanoparticles and its ability to induce oxygen
radicals, OS, and inflammation [24]. A review deals with
the mammalian toxicity of ZnO nanoparticles, through
inhalation results in ROS generation which plays an im-
portant role in inflammatory response [25]. A 2012 re-
view covers toxicity induced by nanoparticles [26]. Mul-
tiwalled carbon nanotubes induce OS, with increased
ROS production and depletion of intracellular GSH.
Multiwalled carbon nanotubes also induce a fibrogenic
response by stimulating ROS production [27]. Data showed
that exposure of cultured RAW 264.7 cells and A549
human lung cells to multiwalled carbon nanotubes led to
OS induced cytotoxicity [28].
3.2. Role of Organic Toxins
OS and oxidative effects on DNA are increased in
mice exposed to styrene or styrene oxide, and these may
play a role in the lung tumorigenesis [29]. In a related
study N-acetylcysteine and GSH were shown to act as
AOs in preventing OS in mice exposed to styrene [30].
Chlorobenzene and 1,2-dichlorobenzene cause OS and
induce apoptosis in lung epithelial cells at non-acute
toxic concentrations [31]. 2-Chloroethyl ethyl sulfide, a
sulfur mustard, causes a significant increase in mito-
chondrial dysfunction, involving increase in ROS in lung
cell injury [32]. Metalloporphyrin acts as an AO in de-
creasing mitochondrial ROS, DNA oxidation and the
increasing intracellular GSH. A study revealed diallyl
trisulfide, a major constituent of garlic oil, induces apop-
tosis of U937 human leukemia cells by generation of
ROS [33].
Research showed that wood dust from pine, birch and
oak is cytotoxic, being able to increase the production of
ROS [34].
4. DERMAL TOXICITY
Insults to the skin may be mild, serious or lethal.
Various constituents of the skin may be affected by der-
mal toxicants. Cutaneous damage may also result from
inhalation or ingestion of toxins, in addition to direct
skin contact. Similarly, substances that induce toxicity
through absorption by the skin can also migrate to and
adversely affect other organs.
In this review, we draw lines of evidence to support
the concept that the ET-ROS-OS unifying theme, which
has been successful in describing the means by which
many other classes of toxins induce their effects, can also
be applied to dermatotoxins [35]. Such toxin classes in-
clude a variety of structurally diverse substances.
Exposure to the chemical warfare agent sulfur mustard
is reported to cause depletion of GSH, which plays an
important role in sulfur mustard-linked OS and skin in-
jury. Cultured skin epidermal cells and SKH-1 mouse
skin when exposed to 2-chloroethyl ethyl sulfide, an
analog of mustard gas, led to amelioration by GSH and
induction of toxicity [36]. N-Acetyl cysteine, a GSH
analog, acts as an AO and shows both protective and
therapeutic effects. The sulfur mustard analog 2-
chloethyl ethyl sulfide induced oxidative DNA damage
in skin epidermal cells and fibroblasts [37]. A related
study also revealed that the sulfur mustard analog in-
duces OS and activates transcription factors AP-1 and
NF-κB via upstream signaling pathways including
MAPKs and Akt in SKH-I hairless mouse skin [38].
Cr(IV) induced apoptosis with involvement of reactive
oxidants [39]. Data indicated that topical exposure to
unpurified single walled carbon nanotubes induced free
radical generation, OS, and inflammation, depletion of
glutathione, oxidation of protein thiols and carbonyls,
elevated myeloperoxidase activity and skin thickening
[40]. Amorphous nanosilica induces endocytosis-de-
pendent ROS generation and DNA damage in human
keratinocytes [41]. Cytotoxicity of uranium, has been in
the spotlight in recent decades. Uranyl acetate induces

P. Kovacic, R. Somanathan / Open Journal of Preventive Medici ne 3 (2013) 32-41 35
OS [42].
Carotenoids are known to be potent quenchers of
singlet molecular oxygen. Solar light-induced photooxi-
dative stress causes skin photoaging by accelerating the
generation of ROS. Intake of carotene lowered the met-
alloproteinase family which is responsible for wrinkles
and sagging of skin, and helps in slowing down ultravio-
let-A-induced photoaging in human skin by acting as a
singlet oxygen quencher [43]. A 2012 review deals with
protective mechanisms of green tea AOs polyphenols in
skin [44]. Another article deals with the ROS-mediated
skin damage and skin protection by AOs [45].
5. NEPHROTOXICITY
Toxic processes have been implicated in the patho-
genesis of several systemic diseases including kidney,
which induces OS in the kidney [46]. A 2012 review
summarizes the induction of OS in kidney [46]. Much of
the nephrotoxicity can be attributed to OS-induced by
drugs, and reports address the role of prescription drug-
induced OS and toxicity [47,48].
Drug-induced OS is implicated as a mechanism of
toxicity in numerous organs, including liver. Well char-
acterized drugs associated with OS, include cancer
therapies, anti-inflammatory drugs, antiviral agents, an-
tipsychotics and analgesics [48]. Metabolism of a drug
may generate a reactive intermediate that can induce
ROS generation, leading to OS in various organs. Cis-
platin is an example of a drug that exhibits multi organ
toxicity, acting as an antineoplastic agent. Clinically,
renal injury has been described. The kidney accumulates
cisplatin to a greater degree than other organs [48]. The
disproportionate accumulation of cisplatin in kidney tis-
sue contributes to free radical generation, depletion of
antioxidants leading to OS and nephrotoxicity [48,49].
Research also indicated that cisplatin nephrotoxicity is
associated with mutual mitochondrial/lysosomal poten-
tiation (cross talk) of OS in renal proximal tubular cells
[50]. This cross-talk results in release of lysosomal di-
gestive protease and phospholipases and mitochondrial
permeability transition pore opening leading to cyto-
chrome c release and activation of caspase cascade,
which signals apoptosis.
Several reports exist for AO action against cisplatin neph-
rotoxicity. Selenium nanoparticles functionalized with 11-
mercapto-1-undecanol inhibit ROS-mediated apoptosis [51].
Captopril, an angiotensin-converting enzyme inhibitor
containing the sufhydryl group can protect against cis-
platin-induced nephrotoxicity in rats [52]. Canabidiol
attenuates cisplatin-induced nephrotoxicity by decreasing
OS, inflammation and cell death [53].
Data demonstrate a key role of lysosomal iron and
early ROS production in gentiomicin-induced lysosomal
membrane premeabilization and apoptosis [54]. Salicylic
acid was found to attenuate the nephrotoxicity in rats
[55]. Ifosfamide, an antineoplastic drug, causes severe
nephrotoxicity. The metabolite chloroactaldehyde is be-
lieved to be the chemical responsible for the nephrotox-
icity [56]. N-Acetyl cysteine acts as an AO in decreasing
the nephrotoxicity. A study showed that ROS, OS, and
MAPK signaling is involved in promoting cyclosporine-
induced glomerular dysfunction and subsequent nephro-
toxicity [57].
Increased production of ROS by anticancer drugs
trichostatin and 5-aza-deoxycytidine, has been described
in patients with various malignancies, which is attributed
to their nephrotoxicity.
A study showed uric acid attenuates toxicity by pre-
venting systemic and renal oxidative stress and tissue
damage induced by mercuric chloride in rats [58]. Cad-
mium (Cd) is a well known human carcinogen and potent
nephrotoxin. Cd caused renal toxicity by inducing lipid
peroxidation and morphological alterations [59]. Curcu-
min, a natural product from turmeric protects Cd-induced
nephrotoxicity in rats. Colistin (polymyxin E), a cationic
polypeptide antibiotic, causes OS-induced nephrotoxicity.
Melatonin was found to attenuate colistin-induced neph-
rotoxicity in rats [60]. Zinc oxide and cadmium sulfide
nanoparticles generate ROS that leads to OS-induced
nephrotoxicity [61].
6. CARDIOVASCULAR TO XICITY
As described in drug-induced OS and nephrotoxicity,
many antibiotic drugs also induce cardiotoxicity [48,62].
The antineoplastic activity of doxorubicin is mediated by
interaction with DNA [48]. Reduction of doxorubicin by
one electron via mitochondrial reductase may generate
anthracycline semiquinone free radicals that produce
ROS [48]. Reaction between iron and doxorubicin may
also generate ROS. Extensive data have been generated
in numerous model systems showing that administration
of AOs protects cardiomycetes from doxorubicin-in-
duced damage. The range of molecules explored is di-
verse, including plant extracts, vitamins C and E, N-
acetylcycteine, L-carnitine, beta-blocker carvedilol, co-
enzyme Q10, and dexrazonxane [48,63].
Adriamycin is another antineoplastic anthracycline
used to treat solid tumors and various forms of cancer,
but it displays cardiac toxicity [64]. Adriamycin is well
known to produce large amounts of ROS, which may be
lethal to cancerous cells. However, unchecked ROS gen-
eration typically leads to OS. Adriamycin has been docu-
mented to cause oxidative damage in several organs,
including heart [64]. Gamma-glutamycysteine ethyl ester
was found to suppress the OS induced by adriamycin.
Several reviews deal with the mechanism and protection

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36
in anthracycline-induced cardiotoxicity [65-68].
Platinum-based compounds are commonly used cyto-
toxic agents in the treatment of several solid tumors.
However, their application is still limited in elderly pa-
tients, due to the risk in cardiovascular toxicity. The in-
creased risk is mainly due to ROS production [69]. AOs
have been involved in cancer treatment by their property
to suppress the oxidant injury [69,70].
Administration of glucose degradation products in-
creased cardiovascular damage in rat models [71]. A
related study showed that glucose degradation products
and advanced glycation end (AGEs) products play a role
in the pathophysiolgy of cardiotoxicity [72]. Mechanistic
aspects of AGEs have been addressed [73].
Cocaine is one of the most common illicitly used
drugs in the world and causes the most frequent drug-
related deaths in young adults. Chronic cocaine con-
sumption is associated with serious cardiovascular com-
plications. Chronic cocaine administration causes severe
myocardial OS through increased ROS production [74].
Cocaine cardiotoxicity may be mediated indirectly through
its sympathomimetic effect, inhibiting reuptake and in-
creasing the levels of neuronal catecholamines.
Exposure to nanoparticles significantly impairs endo-
thelium-dependent vasoreactivity in coronary arterioles,
and this may be due in large part to increases in mi-
crovascular ROS [75]. Another study showed that expo-
sure to ambient particulate pollution induces arrhythmia
via OS and calcium calmodulin kinase II activation [76].
In recent years two reviews have appeared dealing
with heavy metal (Ar, Pb, Cd, Hg) poisoning and car-
diovascular disease. The reviews implicate ROS and OS
as major players in the pathophysiology of atherosclero-
sis [77,78].
7. REPRODUCTIVE TOXICITY
Several earlier reviews have addressed this topic [79-
81]. The present contribution provides recent develop-
ments. There is evidence that several teratogens affect
the developing embryo by increasing OS resulting in
severe embryonic damage. This mechanism seems to
operate in diabetic-induced embryonic damage, as well
as in the mechanism of teratogenicity caused by ionizing
radiation, hypoxia, alcohol and cocaine use and cigarette
smoking. Under diabetic conditions, there was a signifi-
cant decrease in the activity of endogenous AO enzymes
and of vitamins C and E in the embryos. Human and
animal studies show that the main mechanism of fetal
damage induced by high levels of ionizing irradiation,
cocaine and alcohol abuse, hypoxia and cigarette smok-
ing is also by increased embryonic OS. Similarly, several
drugs exert their teratogenic activity via embryonic OS.
Abnormal placentation may also cause enhanced placen-
tal OS, resulting in embryonic death. Animal studies also
show that a variety of AOs are effective in decreasing the
damaging effects of hightened OS induced by teratogens.
Concurrent administration of chloroamphenicol (CAP) with
multivitamin-haematinics complex (MHC) is a common
practice to cushion anticipated anaemic effects in repro-
ductive toxicity [82]. Alone, MHC treatment markedly
decreased catalase (CAT) and glutathione S-transferase
(GST) activities, whereas it resulted in significant in-
crease in superoxide dismutase (SOD) activity. Signifi-
cant increase in testicular lipid peroxidation and sperm
abnormalities were accompanied by reduction in sperm
number, sperm motility and live-dead ratio in all treat-
ment groups. MHC-induced testicular toxicity occurred
vis OS.
Mequindox (MEQ) is a synthetic antimicrobial che-
mical [83]. A study was designed to investigate the hy-
pothesis that MEQ exerts testicular toxicity by causing
OS. Superoxide dismutase (SOD), reduced glutathione
(GSH) and 8-hydroxydeoxyguananosine (8-OHdG) lev-
els were elevated, whereas the malondialdehyde (MDA)
level was slightly increased. The findings provide evi-
dence in vivo for the formation of free radicals.
Reports document the protective effect of AOs, such
as vitamin E [84] and Ginko biloba [85]. Various studies
on reproductive toxicity deal with the role of metals: Pb
[86], Cr [87,88], and Se [89].
8. MITOCHONDRIA
Mitochondrial OS has long been implicated in normal
aging, and a host of human diseases, including cancer
and neurodegenerative disorders. Mitochondria are the
major source of oxygen free radicals in most cell types.
Low concentrations of ROS can serve as signaling func-
tions, triggering the activation of specific pathways [90].
However, high concentrations of ROS cause lipid per-
oxidation, damage to cell membranes, proteins, and DNA.
Mitochondria are, therefore, a major source of ROS and
a major target of ROS-induced OS and damage. A high
rate of mitochondrial DNA mutation eventually exacer-
bates mitochondrial dysfunction and reduces mitochon-
drial energy production [90].
Under OS conditions, mitochondria release various
pro-apoptoic factors. This release is caused by the per-
meabilization of the mitochondrial outer membrane,
which accompanies the depolarization of the mitochon-
drial intermembrane potential. Aldehydes are generated
during numerous physiological processes. Aldehydes are
highly reactive agents, which form adducts with lipids,
proteins, and DNA, affecting the function of these mac-
romolecules. Aldehyde dehydrogenases are important
enzymes that eliminate toxic aldehydes by catalyzing
their oxidation to non-reactive acids. A review discusses
the mitochobdrial aldehyde dehydrogenase and cardiac
diseases [91]. Inhibition of aldehyde dehydrogenase 2 by

P. Kovacic, R. Somanathan / Open Journal of Preventive Medici ne 3 (2013) 32-41 37
OS is associated with cardiac dysfunction in diabetic rats
[92]. A study demonstrated that TNF-α-induced OS al-
ters redox homeostasis by impairing the membrane per-
meability transition pore opening proteins adenine nu-
cleotide translocator and voltage-dependent anion chan-
nel, thereby resulting in the pore opening, causing mito-
chondrial dysfunction and attenuated cardiac function
[93].
A recent review deals with the mitochondria death/
survival signaling pathways in cardiotoxicity induced by
anthracyclines [94]. Data shows that inhibition of mito-
chondrial transition permeability prevents doxorubicin-
induced cardiotoxicity. OS and mitochondrial dysfunc-
tion have been implicated in atherosclerosis [95]. Au-
thors suggest mitochondria-targeted AOs as potential
therapy. Alzheimer’s disease, the most common form of
dementia with a progressive course, evidences neuronal
damage in specific vulnerable brain regions and circuits
involved in memory and language [96]. Two recent re-
views deal with mitochondrial- and endoplasmic reticu-
lum-associated OS in Alzheimer’s disease [96,97].
There is an emerging consensus that aging is a multi-
factorial process, which is genetically determined and
influenced epigenetically by environment. OS induced
DNA damage, oxidation of proteins, lipid peroxidation
and ROS have been implicated as causative factors of
aging [98]. Two reviews deal with the OS, mitochondrial
dysfunction and aging [98,99].
9. CONCLUSION
This review presents recent reports dealing with elec-
tron transfer, reactive oxygen species and oxidative
stress as part of the mechanism of toxicity involving or-
gans in human health. Various portions of the organ cells
may be involved in the insults. Antioxidants may play a
role in prevention.
10. ACKNOWLEDGMENTS
Editorial assistance by Thelma Chavez is acknowledged.
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ABREVIATIONS
OS, oxidative stress;
ROS, reactive oxygen species;
RNS, reactive nitrogen species;
ET, electron transfer;
AO, antioxidant;
COPD, chronic obstructive pulmonary disease;
GABA, gamma amino butyric acid;
HSP, heat shock proteins;
LPP, lipid peroxidation products;
CIS, cisplatin;
SOD, superoxide dismutase;
GSH, glutathione;
8-OHdG, 8-hydroxydeoxyguanosine;
MDA, malondialdehyde;
MEQ, Mequindox.