ArticlePDF AvailableLiterature Review

Abstract

N-acetyl cysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant in vivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis. It acts directly as a scavenger of free radicals, especially oxygen radicals. NAC is a powerful antioxidant. It is also recommended as a potential treatment option for different disorders resulted from generation of free oxygen radicals. Additionally, it is a protected and endured mucolytic drug that mellows tenacious mucous discharges. It has been used for treatment of various diseases in a direct action or in a combination with some other medications. This paper presents a review on various applications of NAC in treatment of several diseases.
CELL JOURNAL(Yakhteh), Vol 19, No 1, Apr-Jun (Spring) 2017 11
Review Article
A Review on Various Uses of N-Acetyl Cysteine
Vida Mokhtari, M.Sc.1, 2, 3, Parvaneh Afsharian, Ph.D.2, Maryam Shahhoseini, Ph.D.2,
Seyed Mehdi Kalantar, Ph.D.1, Ashraf Moini, M.D.3, 4*
1. Department of Molecular Cytogenetics, Research and Clinical Center for Infertility, University of Medical Sciences,
Yazd, Iran
2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, Iran
3. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for
Reproductive Biomedicine, ACECR, Tehran, Iran
4. Department of Obstetrics and Gynecology, Roointan-Arash Hospital, Tehran, Iran
*Corresponding Address: P.O.Box: 16635-148, Department of Endocrinology and Female Infertility, Reproductive
Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Email: a_moini@royaninstitute.org
Received: 19/Dec/2015, Accepted: 7/May/2016
Abstract
N-acetyl cysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant in
vivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation
biosynthesis. It acts directly as a scavenger of free radicals, especially oxygen radicals.
NAC is a powerful antioxidant. It is also recommended as a potential treatment option for
different disorders resulted from generation of free oxygen radicals. Additionally, it is a
protected and endured mucolytic drug that mellows tenacious mucous discharges. It has
been used for treatment of various diseases in a direct action or in a combination with
some other medications. This paper presents a review on various applications of NAC in
treatment of several diseases.
Keywords: N-Acetyl Cysteine, Antioxidant, Oxidative Stress
Cell Journal(Yakhteh), Vol 19, No 1, Apr-Jun (Spring) 2017, Pages: 11-17
Citation: Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A review on various uses of N-acetyl
cysteine. Cell J. 2017; 19(1): 11-17.
Introduction
N-acetyl cysteine (NAC), as a safe and
inexpensive medication, is commercially accessible
since long-time ago (1). This drug is not found in
natural sources, although cysteine is present in some
meals like chicken and turkey meats, garlic, yogurt,
and eggs (2). NAC is a well-tolerated mucolytic
drug that moderates clinging mucous secretions
and enhances glutathione S-transferase activity.
During oral administration, deacetylation reaction
of NAC happens while passing along the small
intestine as well as liver, thus its bioavailability is
decreased to 4-10%. NAC stimulates glutathione
biosynthesis, promotes detoxication, and acts
directly as a scavenger of free radicals. It is a
powerful antioxidant and a potential treatment
option for diseases characterized by the generation
of free oxygen radicals (3). Studies have shown no
maternal or fetal harmful effects of NAC treatment.
This nutritional supplement is an excellent source
of sulphydryl groups. NAC prevents apoptosis and
oxygen related genotoxicity in endothelial cells by
increasing intracellular levels of glutathione and
decreasing mitochondrial membrane depolarization
(4). The critical antioxidant power of NAC is due to
its role as a precursor of glutathione, which is one of
the most important naturally occurring antioxidants
(5). NAC combination with vitamin E, or vitamins
A+E, as well as essential fatty acids considerably
reduce reactive oxygen species (ROS), leading
to pregnancy rate improvement (6). Studies have
indicated that preserving impact of NAC against
the toxicity of chemicals is due to its dual role as a
nucleophile and as a -SH donor (7). In this study by
reviewing literatures, various applications of NAC
in treatment of some diseases are highlighted.
Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is one of the
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Various Applications of NAC
most common endocrine glands-related diseases
affecting 5-10% of reproductive-age women (8). This
syndrome is considered as the most common cause
of anovulatory infertility. PCOS is also associated
with pregnancy complications such as recurrent
pregnancy loss (RPL). Different studies report the
prevalence of PCOS in women with a history of
RPL in a wide range of 10-82%. Findings show that
70.7% of PCOS women with a previous RPL had
thrombophilic disorders. In addition, prevalence of
protein C deciency is signicantly higher in PCOS
patients compared to the non-PCOS women (9).
The results of a study showed that women with
PCOS have a high prevalence of metabolic syndrome
and its individual components (obesity, hypertension,
glucose intolerance and triglycerides), particularly
decreased high density lipoprotein cholesterol (10). In
another study, women and their relatives with PCOS
had an increased prevalence of diabetes commonly in
mother’s side of the family (11).
As the rst medication option, clomiphene citrate
(CC) is applied for the induction of ovulation in PCOS
women. A collection of published results for treatment
with CC showed a pregnancy rate and a miscarriage
rate of 36 and 20.4%, respectively. One of the
frequently determined problems of this treatment is
resistance to CC in up to 40% of PCOS patients. NAC
is a mucolytic drug with insulin-sensitizing properties
that has been used successfully as a supporting
therapy in subjects with CC-resistant PCOS (8).
Recent studies have shown that a combination of CC
and NAC considerably increased both ovulation and
pregnancy rates in women with CC-resistant PCOS.
NAC has multiple biological effects, two of which
are potentially and directly related to pregnancy rate
improvement. NAC has mucolytic action, thus it can
revoke the negative effect of CC on cervical mucus.
Simultaneously, it has insulin sensitizing effect that
could assist in issues related to PCOS. The negative
inuence of CC on cervical mucus can create a
"hostile" environment for conception (1).
Researchers evaluated the effect of NAC, known
to resupply stores of the antioxidant glutathione, on
insulin secretion and peripheral insulin resistance
in subjects in association with PCOS. Moreover,
treatment of hyperinsulinemic patients by NAC
was found to tailor control parameters of glucose
in them and consequently, their insulin levels and
peripheral insulin sensitivity were reduced and
increased, respectively. Therefore, the antioxidant
effects of NAC may act as a therapeutic approach
to improve the level of circulating insulin as
well as insulin sensitivity in PCOS patients with
hyperinsulinemia (12).
Premature birth and recurrent pregnancy loss
Premature birth is the most common reason of
perinatal mortality and long-term unhealthiness
in low-income countries (13). Inammation,
fetal infection, and previous preterm delivery
are signicant risk factors for preterm birth and
neonatal brain injury (14). Rising infection with
bacterial vaginosis during pregnancy is related
to a risk factor for preterm delivery and low birth
weight. Antimicrobial medical care is, although,
not adequate for the prevention of preterm birth
and the inammatory as well as anti-inammatory
responses could make problem complex (3).
NAC by having an anti-inammatory outcome
can affect human term and preterm labors. NAC
restrains the inammatory response with no
respect whether infection is started before or after
treatment initiation with the drug. Shahin et al. (3)
concluded that in women with previous preterm
birth and bacterial vaginosis, 0.6 g of NAC daily
can be taken orally along with progesterone after
week 16 of pregnancy to protect against preterm
birth recurrence and improve neonatal outcome.
RPL is dened as the occurrence of three or
more consecutive pregnancy losses in the rst or
early second trimester of pregnancy (less than 20
weeks of gestation). It is one of the most common
clinical problems in reproduction that a certain
cause can be found in only 50% of cases (15).
Many etiologies have been suggested for RPL (16).
For example, molecular genetic background for
RPL is being increasingly understood, and some
polymorphisms associated with RPL have been
reported. According to the research directed up
to now, more than 40 gene products distinctively
have been distinguished to be expressed in women
with RPL compared to healthy women. These
genes may have regulatory roles in establishing
or maintaining normal pregnancy. In this manner,
any nucleotide modications in targeted genes
may result in distinct expression and activity
endangering general well-being during pregnancy.
A recent study showed a relationship between
c.179A>C mutation in the Bax promoter and RPL
and also, two polymorphisms, namely c.90G>C
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Mokhtari et al.
and c.95G>A in exon 1, found among patients
that can be considered as genetic factors making
people susceptible to miscarriages (17). Findings
of the other recent study revealed a new genetic
relationship between occurrences of RPL and
SULF1 gene mutation. SULFs are a protein family of
arylendosulfatase. They act as post synthetic editors
that can selectively release 6-O-sulfate groups from
heparin sulfates, consequently changing the sulfation
patterns of proteoglycans and binding site of many
growth factors. With such unique regulatory activity,
SULFs have an important role in many biological
processes, such as angiogenesis, cell signaling
and embryogenesis. In this gene family, SULF1
is expressed in the large number of embryonic
and adult tissues, while it has an important role
in viability and embryonic development (18). In
a study conducted by some researchers, high rate
of mutations in D-loop of mtDNA was observed
in maternal blood, a fact that may have a direct or
indirect role in inducing RPL. This outcome can
be utilized as part of the RPL evaluation, planning
conceivable medications for enhancing the results
of assisted reproduction (19). Some evidence has
shown that oxidative stress might be a contributory
factor in RPL (16). One phenomenon that is
known as a common patho-physiological pathway
for various etiologies of RPL, can be placental
oxidative stress. Amin concluded that NAC is a
well-tolerated drug that could potentially be an
effective treatment in patients with unexplained
RPL. Administration of a combination of NAC
and folic acid, in comparison with folic acid alone,
is resulted in prolongation of a living pregnancy up
to 20 weeks. In addition, combination of NAC and
folic acid were also associated with a signicant
increase in the take-home baby rate, as compared
to folic acid alone (4).
Acetaminophen toxicity
Acetaminophen administration is reported as
the most common drug overdose in pregnancy.
Acetaminophen readily crosses the placenta and
in toxic doses can result in fetal hepatic necrosis,
premature birth, spontaneous abortion, and fetal
death (2). NAC is an amino acid that contains
thiol group. It has been used for the treatment
of acetaminophen toxicity (20). N-Acetyl-p-
benzoquinonimine is a potent oxidative metabolite
of acetaminophen, resulting in hepatotoxicity, if
it is not reduced by glutathione. NAC is thought
to affect through multiple mechanisms including
replenishing glutathione, reducing N-acetyl-p-
benzoquinonimine directly, and performing non-
specic hepatoprotective actions related to its
antioxidant properties. This compound is used
to treat acetaminophen poisoning throughout
pregnancy (3). It is universally effective to prevent
hepatotoxicity, if it is administrated within 10
hours of acetaminophen overdose (21).
In addition, acetaminophen toxicity is a common
cause of drug-induced hepatotoxicity in children
and adults. NAC has been used for several decades
and it has been proven as a counterpoison choice
in treating acetaminophen-induced hepatotoxicity.
There is considerable clinical evidence to support
the fact that oral and intravenous NAC are equally
effective in the prevention of hepatotoxicity. An
important factor in evaluating the effectiveness of
NAC is the timing of therapy commencement in
relation to the administration. Patients that ingest
a severe overdose and have NAC therapy started
within 8 hours get well and have less than a 10% rate
of occurrence of hepatotoxicity. They generally do
not develop liver failure or death. Those patients
who have chronically taken immoderate doses
of acetaminophen over many hours and/or have
NAC therapy started more than 8 hours after an
acute overdose are at a risk of hepatotoxicity with
approximately 8-50% incidence (22).
Several recent studies have investigated the
antioxidant properties of NAC in feto-placental
metabolism (23, 24). NAC appears to attenuate
placental production of inammatory cytokine
interleukin 6 involved in placenta infection
and inammation in the pregnant rat model. A
murine model demonstrated benet of NAC in a
complicated pregnancy, manipulated by infection
and free radical production, suggesting the ability
of NAC to restore maternal and fetal oxidative
balance to reduce preterm birth caused by different
factors such as acetaminophen toxicity (21).
In vitro studies have shown that oxidative stress
might serve as a signal to initiate and propagate
the inammatory process, resulting in apoptosis of
placental tissues (6). Bloosesky et al. (25) showed
that preventative effect of NAC could reduce fetal
inammatory cytokines in response to maternal
lipopolysaccharide. Their results suggested that
prophylactic NAC administered in pregnancies
was associated with a risk of maternal infection/
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Various Applications of NAC
inammation, likely protecting fetus from adverse
inammatory sequelae.
Administration of N-acetyl cysteine for infertile
patients undergoing assisted reproductive
techniques
Elgindy et al. (5) found that 1200 mg NAC (daily)
supplementation, started with administration
of human menopausal gonadotrophin till the
day of human chorionic gonadotrophin, did
not signicantly increase pregnancy rate in
intracytoplasmic sperm injection (ICSI) cycles
using the long agonist protocol. NAC treatment was
associated with insignicant decrease in granulosa
cell apoptosis, as well as insignicant increase in
fertilization rate and grade-one embryo formation.
Larger-scale studies, possibly with higher doses
and/or longer duration of NAC administration,
should be performed to identify any signicant
effects. In addition, Cheraghi et al. (26) conducted
a study to determine the effect of co-administration
of NAC and metformin on ovulation induction in
PCOS patients with ICSI cycle. They detected that
co-administration of these two components has no
benet for ovulation induction in PCOS patients
with ICSI cycle. In another study, Rizk et al. (27)
investigated the effect of NAC on performance of
CC in ovulation induction. They concluded that
the combination of NAC with CC is an effective
way for ovulation induction in young women
undergoing ICSI cycles.
Chronic bronchitis
Chronic bronchitis is dened as the presence
of chronic productive cough for more than
three months in each of two sequential years.
Therefore, an important goal in the treatment of
chronic bronchitis is to decrease the frequency
and duration of intensication, and to decrease
symptoms in patients with aggravations. In some
European countries, mucolytic drugs, particularly
NAC may be used as an anti-inammatory
drug as well as an antioxidant (28, 29). In these
countries, it is believed that NAC can decrease the
frequency of aggravations and improve symptoms
in patients with chronic bronchitis. Recently, a
comprehensive review in literature survey has
concluded in the eld of the effectiveness of any
oral mucolytic drugs that a decline of aggravations,
days of disability and days of antibiotic treatment
was averagely determined in patients with chronic
clogging pulmonary disease (30).
Ulcerative colitis
Ulcerative colitis is a chronic inammatory
disorder which multiple casual factors can affect it.
Human colitis has many similar characteristics to
acetic acid (AA)-induced colitis, as a reproducible
and simple model. Studies have indicated that
some signaling pathways contributing in cell
apoptosis and growth, angiogenesis, redox-
regulated gene expression, and inammatory
response can be affected by NAC (6, 31-33).
Therefore, NAC may not only protect against
the direct detrimental impacts of oxidants, but
also advantageously modify inammatory events
in colitis (34). The benecial inuences of NAC
were related to the changes including: i. Softened
colonic injury, ii. Decreased oxidative stress, iii.
Lowered cell apoptosis, iv. Increased recovery of
the injured colon, and v. Increased formation of the
tight junction (6).
Liver cancer
Liver cancer is one of the most common life-
threatening malignancies, all over the world
and up to now, there is no effective drug for
the treatment of liver tumors (35). Although,
interferon (IFN) is the most applied medication
in chronic hepatitis and hepatocarcinoma, due to
its immune response activation property and also
regulation of differentiation and cell growth (36).
NAC, as an enhancer of glutathione biosynthesis
(37), is one of the frequently used antioxidant
drugs for treatment of liver disorders (38, 39).
Cell culture and animal models have shown that
NAC can preserve normal cells against toxicity of
radiotherapy and chemotherapy, but not cancerous
cells (37). Administration of NAC may play a
role in treatment of some forms of cancer, while
induced damages in DNA can be completely
blocked by NAC (38).
Muscle performance
Investigations showed no effect of NAC on non-
fatigued muscle, although after three minutes of
repetitive contractions, it caused a considerably
enhanced force output, up to approximately
15%. This means that NAC can improve muscle
performance. This result is originated from the
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Mokhtari et al.
fact that oxidative stress plays a causal role in the
fatigue process, since NAC is a scavenger of free
radicals causing oxidative stress. It has been well-
reported that infusion of NAC can be effective
on enhancing the overall redox status in vivo. It
has also been shown that NAC infusion could
minimize the muscle fatigue (40).
Hemodialysis
Homocysteine (Hcy) is a sulphur-containing
amino acid that is produced in body, by the
metabolism of the methionine amino acid
(41). Hcy level in patients with hemodialysis
is associated with kidney-related disorders.
However, in the treated hemodialysis patients,
some studies have shown that NAC administration
could affect plasma Hcy levels. There are some
reports indicating that NAC, with an antioxidant
property, has declined plasma Hcy level in the end
stage renal disease (ESRD) patients undergoing
hemodialysis. Although, lower dosage of NAC (for
example, 600 mg/day for a period of one month)
could not help to decrease Hcy plasma levels in
these patients (42).
Asthma
Asthma is a chronic disorder associated with
inammation and immune cell inltration of
airways (43). Airway hyper-responsiveness
(AHR) can be originated from consistent presence
of inammatory mediators and immune cells
in airways. AHR is clinically determined with
breathlessness, coughing and wheezing symptoms
(44). Studies showed the preventive effect of
NAC antioxidant on the AHR and steroid resistant
accumulation of inammatory cells in the airways
of the animal model with acute exacerbation of
asthma (45-47).
Alzheimer
Alzheimer disease (AD) is known as a
multifactorial disease with many abnormalities
in physiological, biochemical, and neurochemical
point of view. Aging is the major risk factor for
AD that coexists with other causes of cognitive
decline, particularly vascular dementia (48).
Some factors, such as mitochondrial dysfunction,
abnormal protein aggregation, metal accumulation,
inammation and excitotoxicity play important
roles in AD pathology. Although the relationship
between these factors and development of AD is
multidirectional, oxidative damage is considered
as a common thread linking some of these factors
(49). Results of different studies showed that
lipoic acid (LA) and NAC decreased levels of
oxidative and apoptotic markers via protection of
mitochondrial function (50-53). Combination of
both LA and NAC maximizes this protective effect
suggesting that this may prevent mitochondrial
decay associated with aging and age-related
disorders such as AD. Antioxidant therapies based
on LA and NAC seem promising since they can
act on mitochondria, one key source of oxidative
stress in aging and neurodegeneration (50).
Parkinson
Parkinson disease (PD) is a very prevalent
neurodegenerative disorder caused by unknown
deterioration of cells which generate dopamine
in the pars compacta, a part of the substantial
nigra located in the midbrain (54). In terms of
pathogenesis, PD appears to be multi-factorial
disorder, including environmental factors, acting
on genetically vulnerable individuals when they
are older (55, 56). A wide range of both genetic
and environmental factors have been proposed as
contributing to the initiation and progression of
PD, but aging is the single most important risk
factor for this disorder and undoubtedly interferes
in PD progression through its accumulative
oxidative damage, decrease in antioxidant ability
and impairment of mitochondrial bio-energetic
capacity in the brain (57, 58). Taking into account
that most of PD patients experience accumulative
oxidative damage, some clinical studies have
demonstrated the controversial effect of some
antioxidant administrations -such as NAC- on
treatment of PD (59-61). Some improvements have
been reported for systemic administration of NAC
in animal models, such as: i. Enhancement of brain
level of glutathione, ii. Reduction of oxidative
damage-markers, iii. Enhancement of brain
synaptic and non-synaptic brain mitochondrial
complex I activities, and iv. Protection against
dopamine-induced cell death (59).
Conclusion
A review on NAC literature shows that this
agent is a safe and well-tolerated supplementary
drug without any considerable side effects. It
CELL JOURNAL(Yakhteh), Vol 19, No 1, Apr-Jun (Spring) 2017 16
Various Applications of NAC
is as an antioxidant with a free radical scavenger
property, as important characteristic of this medical
supplement. It has been used as a benecial drug
treatment for some disorders such as poly cystic
ovary syndrome patients with CC resistance,
preterm birth, acetaminophen toxicity, RPL, chronic
bronchitis, ulcerative colitis, liver cancer, muscle
performance, hemodialysis, asthma, Alzheimer
and Parkinson. Although in some cases, such as
improving pregnancy rate in ICSI cycles, NAC
action is still unclear and further investigations are
necessary.
Acknowledgments
The authors would like to thank Royan Institute
experts for their helpful comments and sugges-
tions. There is no conict of interest in this study.
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... [ [109][110][111] Activated protein C Anti-inflammatory, anti-apoptotic ...
... N-acetyl cysteine (NAC) is a precursor of L-cysteine and a powerful antioxidant. Cysteine, which can be obtained from diets such as chicken, turkey, dairy products, eggs, and garlic, exhibits antioxidant properties such as helping to scavenge ROS and having therapeutic effects for functional disorders caused by free radicals [111]. The level of cysteine, one of the three amino acids used in the synthesis of glutathione, is increased by NAC, promoting glutathione production, and thus increasing glutathione levels also reduces oxidative stress [110,111]. ...
... Cysteine, which can be obtained from diets such as chicken, turkey, dairy products, eggs, and garlic, exhibits antioxidant properties such as helping to scavenge ROS and having therapeutic effects for functional disorders caused by free radicals [111]. The level of cysteine, one of the three amino acids used in the synthesis of glutathione, is increased by NAC, promoting glutathione production, and thus increasing glutathione levels also reduces oxidative stress [110,111]. It has been demonstrated that the decrease in glutathione levels seen in mood swings including depression and bipolar disorder can be improved by reducing the symptoms related to the disease after treatment with NAC [109]. ...
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The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood–brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain’s immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.
... It can be utilized in several therapeutic conditions, including drug addiction, bronchitis, schizophrenia, and acetaminophen toxicity. NAC works as a precursor that is transformed into cysteine by aminoacylase-1 in the intestine and then absorbed into the blood circulation (Mokhtari et al., 2017). Because cysteine is an essential part of glutathione, NAC supplementation replenishes glutathione stores. ...
... As depicted in Figure 4E-F, H2O2 significantly increased the intracellular 4-HNE and MDA, while CIP effectively reduced their levels. In the above study, we used N-acetyl cysteine (NAC), a commonly used antioxidant, as a positive agent [41] . As expected, NAC markedly reduced ROS accumulation as well as the levels of 4-HNE and MDA (Figure 4A-F). ...
... It may be of interest whether the intake of some drugs with anti-oxidative and anti-inflammatory properties could neutralize the later development of neuropsychiatric disorder-related consequences. For example, N-acetylcysteine (NAC) might be suggested as a supplement for high-risk pregnancies, as it may considerably improve neonatal consequences [20]. Taken together, the poly I:C model animal might be useful for studying the developmental factors that may alter multisensory integration in neuropsychiatric disorders [21]. ...
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Neuropsychiatric disorders are a public health concern, in which diagnosis and prognosis may be based on clinical symptoms that might often diverge across individuals. Schizophrenia is a major neuropsychiatric disorder, which may affect millions worldwide. However, the biochemical alterations of this disorder have not been comprehensively distinguished. In addition, there is less confidence in finding specific biomarkers for neuropsychiatric disorders, including schizophrenia, but rather a specific characteristic behavioral pattern. In general, maternal immune activation is considered to be one of the important factors in the development of neuropsychiatric disorders. Here, a mouse model of neuropsychiatric disorders was created, in which poly I:C, sodium dextran sulfate (DSS), and κ-carrageenan (CGN) were utilized for maternal immune activation during the pregnancies of mother mice. Subsequently, we examined the link between biochemical changes in p62 and/or glutamate aspartate transporter (GLAST) in the brains of offspring mice and the alteration in their experimental behavior scores. Furthermore, a therapeutic study was conducted on these neuropsychiatric disorder model mice using butyric acid, piceid, and metformin. It was found that some molecules could effectively improve the behavioral scores of neuropsychiatric model mice. Importantly, significant correlations between certain behavioral scores and p62 protein expression, as well as between the scores and GLAST expression, were recognized. This is the first report of a significant correlation between pathological behaviors and biochemical alterations in neuropsychiatric disorder model animals. This concept could contribute to the development of innovative treatments to at least ameliorate the symptoms of several psychiatric disorders.
... N-acetylcysteine (NAC) is an amino acid derived from the N-acetylation of L-cysteine. Studies have demonstrated that NAC can play an antioxidant role and it has been used to treat many diseases [12], including lung diseases [13] such as chronic obstructive pulmonary disease (COPD) [14] and bronchial asthma [15]. Mohanty et al. found that NAC may inhibit the cytokine storm after coronavirus disease 2019 (COVID-19) infection, thereby reducing the lesion and enhancing the prognosis [16]. ...
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Introduction: The purpose of this study was to observe the effect of N-acetylcysteine (NAC) on oxidative stress (OS), intracellular Mycobacterium tuberculosis (MTB) load, apoptosis, and autophagy of macrophages infected with H37Rv MTB. In addition, we explored the possible mechanism of action, to provide a rationale for the use of NAC in the treatment of tuberculosis. Methodology: We divided THP-1 macrophages into four groups: control, control + NAC, H37Rv, and H37Rv + NAC. OS, apoptosis, autophagy and intracellular MTB colony-forming unit (CFU) indexes were measured at 0, 4, 24, and 48 hours, respectively. Then, various indicator changes were systematically compared. Results: The levels of reactive oxygen species (ROS), malondialdehyde (MDA), apoptosis rate, and LC3II/ β-actin ratio in the H37Rv group increased at 4 hours and reached their peak at 48 hours. The ROS and MDA in the H37Rv + NAC group were lower than those in the H37Rv group. CFU in the H37Rv + NAC group increased at 24 hours and decreased at 48 hours after treatment with NAC, relative to the H37Rv group. In addition, the H37Rv + NAC group showed a decrease in LC3II/β-actin ratio 48 hours after NAC treatment, compared to the H37Rv group. Conclusions: MTB infection can lead to an increase in macrophage OS, apoptosis, and autophagy levels. However, after treatment with NAC, the growth of MTB in macrophages is inhibited, and OS and autophagy levels are reduced. The antioxidant effect and inhibitory effect of NAC on MTB are related to MTB-mediated macrophage OS and autophagy.
... It inhibits ROS via free-radical scavenging with a redox potential of its thiol group or by stimulating GSH biosynthesis. This promotes detoxification and presents a potential treatment option for diseases characterized by the generation of free oxygen radicals [40,41] Studies have shown that it reduces ROSmediated oxidative damage of DNA [42]. ...
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Oxidative stress stemming from distortions in the balance between reactive oxygen species (ROS) and antioxidants, plays a leading role in the pathophysiology of male reproductive dysfunction. A convincing body of evidence emphasizes on the importance of oral antioxidant therapy in the management of male sub- or infertility. As such, the focus of this review is to present recent evidence assessing the in vivo effects of conventional and traditional antioxidant remedies on male reproductive function with a special emphasis on oral delivery of the substance and rats as the leading animal model in biology and medicine.
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Introduction : Recurrent pregnancy loss (RPL) is a critical medical problem in about 0.5-2% of women. The molecular genetic background for spontaneous abortion is being increasingly understood, and some polymorphisms associated with it have been reported. This study investigates alterations of the Bax gene as a pro-apoptotic gene in women with idiopathic RPL. Material and methods : The frequency of mutations in the Bax gene of 67 idiopathic RPL women was studied in comparison to a sample of 70 healthy women. The promoter and the entire coding regions (exons 1-7) were amplified using polymerase chain reaction (PCR). The purity of the PCR product was first verified by electrophoresis on a 2% agarose gel. The amplified fragment was then sequenced by automated DNA sequencing. Results : A statistically significant difference was observed between patients and the control group regarding the frequency of alleles A(-179)G in the Bax promoter region (p = 0.013). Also among patients, G90C and G95A transitions were found in the coding region of exon 1 that change amino acid glutamine (Q) to histidine (H) and arginine (R) to lysine (K), respectively. A statistically significant association was observed between H allele (p = 0.0001) and K allele (p < 0.0001) and the occurrence of RPL. Conclusions : Our results indicate an association between A(-179)G mutation in the Bax promoter and RPL. Moreover, two polymorphisms, G90C and G95A in exon 1, found among our patients, could be considered as genetic factors making people susceptible to miscarriages. According to our findings, the Bax gene has an important role in pregnancy loss and the variations of this gene could help in the assessment of RPL.
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Oxidative stress appears to have an important role in glucocorticoid insensitivity, as a crucial problem in asthma therapy. We studied the preventive effect of antioxidant N-acetylcysteine (NAC) on the airway hyper-responsiveness (AHR) and the accumulation of inflammatory cells in the airways in an animal model of steroid resistant acute exacerbation of asthma. Systemically sensitized Balb/C mice were exposed to Ovalbumin aerosol on days 13, 14, 15 and 16, followed by intratracheal lipopolysaccharide (LPS) to induce acute exacerbation. NAC (intraperitoneal, 320 mg/kg 30 min before and 12 hours after each challenge) reduced hyperresponsiveness with/out dexamethasone. LPS application caused neutrophilia in bronchoalveolar lavage fluid (BALF) and eosinophil count was higher than respective control in BALF as well as neutrophils after dexamethasone treatment. NAC significantly decreased neutrophil and eosinophil count in BALF as well as inflammatory cytokines (IL-13 and IL-5).We concluded that addition of NAC to asthma therapy has beneficial preventive effects in an animal model of steroid resistant acute exacerbation of asthma.
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Background: Polycystic ovarian syndrome (PCOS) is a condition associated with chronic anovulation, insulin resistance and androgen excess. Women with this syndrome are at increased risk of metabolic syndrome. Objective: The aim of the present study was to determine the prevalence of metabolic syndrome (MBS) in women with PCOS referred to Arash Hospital in different ages and body mass index (BMI). Materials and Methods: A cross-sectional study was conducted in Gynecologic Clinic at Arash Hospital affiliated with Tehran University. A total of 282 women with PCOS ages between 15-40 years were included. The prevalence of Metabolic Syndrome and its components in this population were the main outcomes. Height, weight, waist circumference, blood pressure and laboratory tests (FBS, TSH, HDL-C, serum prolactin, triglycerides and total cholesterol) were measured in this population. Results: The prevalence of MBS in PCOS women was 22.7% (64 cases). The rate of central obesity, FBS more than 110 mg/dl, triglycerides more than 150 mg/dl, high-density lipoprotein cholesterol levels (HDL-C) less than 50 mg/dl, and blood pressure ≥130/85 mmHg in PCOS women was 31% (87), 3.2% (9), 33% (93), 68.8% (194), and 10.6% (30), respectively. The risk of MBS was increased in older and the obese women (BMI ≥30 kg/m2). Conclusion: The present sample showed women with PCOS have a high prevalence of MBS and its individual components, particularly decreased HDL-C.
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There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht-Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage.
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Objective: N-acetyl-cysteine (NAC) has been shown to enhance the action of clomiphene citrate in ovulation induction. The objective of this study was to examine the use of NAC with clomiphene citrate for ovarian stimulation in assisted conception as a model for "Friendly IVF" Design: pilot study Materials and methods: Twenty infertile patients undergoing IVF/ICSI cycles were offered NAC, 1,200 mg/day from day 3-7 of the menstrual cycle with CC (100 mg/day) starting on day 3-7. hCG (10,000 IU) was given when leading follicle(s) were ≥ 18mm followed by ICSI. Main outcome measure(s): clinical pregnancy rate was the primary outcome and implantation rate, number of oocytes retrieved, fertilization rate were secondary outcomes Result(s): response to CC stimulation with NAC co-treatment was evident by a number of mature follicles ranging from 2-7 at the time of hCG administration. Clinical pregnancy was achieved in 4 cycles (20%). Conclusion(s): In this preliminary report, a potential benefit of NAC co-treatment with CC in young women undergoing IVF/ICSI cycles was demonstrated. This combination provides a cheap, effective way for ovulation induction in an IVF setting compatible with the concept of friendly IVF
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Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the α-synuclein protein in the form of Lewy bodies and Lewy neurites are neuropathological hallmarks of Parkinson's disease. Most cases occur sporadically, but mutations in several genes, including SNCA, which encodes α-synuclein, are associated with disease development. The discovery and development of therapeutic strategies to block cell death in Parkinson's disease has been limited by a lack of understanding of the mechanisms driving neurodegeneration. However, increasing evidence of multiple pivotal roles of α-synuclein in the pathogenesis of Parkinson's disease has led researchers to consider the therapeutic potential of several strategies aimed at reduction of α-synuclein toxicity. We critically assess the potential of experimental therapies targeting α-synuclein, and discuss steps that need to be taken for target validation and drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Cysteine could potentially lower the risk of stroke through antihypertensive and antioxidant effects. Our aim was to evaluate the hypothesis that cysteine intake is inversely associated with stroke incidence. We used data from the Swedish Mammography Cohort, a population-based prospective cohort of 34 250 women who were free of cardiovascular disease and cancer and had completed a food-frequency questionnaire about diet and other risk factors for stroke in the autumn of 1997. Stroke cases were identified by linkage of the study population with the Swedish Inpatient Register and the Swedish Cause of Death Register. Relative risks (RR) with 95% confidence intervals, adjusted for potential confounders, were estimated by using Cox proportional hazards regression model. We ascertained 1751 incident cases of stroke during 10.4 years of follow-up. Dietary cysteine intake (mean, 635 mg/d) was inversely associated with stroke risk. The multivariable RR of total stroke comparing the highest with the lowest quintile of cysteine intake was 0.79 (95% confidence interval, 0.65-0.97; P for trend=0.04). The corresponding RR was 0.82 (95% confidence interval, 0.65-1.03; P for trend=0.12) for cerebral infarction and 0.54 (95% confidence interval, 0.29-1.03; P for trend=0.08) for intracerebral hemorrhage. Dietary intake of other amino acids showed no independent (after adjustment for cysteine intake) association with stroke risk. These findings suggest that dietary cysteine intake may be inversely associated with risk of stroke. http://www.clinicaltrials.gov. Unique identifier: NCT01127698. © 2015 American Heart Association, Inc.