Beneficial Effects Of N-acetylcysteine Research Articles

N-acetylcysteine ameliorates repetitive/stereotypic behavior due to its antioxidant properties without activation of the canonical Wnt pathway in a valproic acid-induced rat model of autism.

N-acetylcysteine (NAC) is widely used as an antioxidant, and previous studies have suggested that it may have potential as an alternative therapeutic strategy for the treatment of patients with autism. However, the exact effects of NAC administration on the development of autism, as well as the molecular mechanisms underlying its actions, have yet to be fully elucidated. The present study aimed to investigate the effects of NAC on the oxidative status of rats in a valproic acid (VPA)‑induced model of autism, and to examine the involvement of the canonical Wnt signaling pathway in the actions of NAC. Rats exposed to VPA were monitored for behavioral changes, and oxidative stress indicators and key molecules of the canonical Wnt pathway were investigated using colorimetric and western blot analysis, respectively. The present results demonstrated that NAC ameliorated repetitive and stereotypic activity in autism model rats. Furthermore, NAC was revealed to relieve oxidative stress, as demonstrated by the increased glutathione and reduced malondialdehyde levels compared with VPA‑treated rats. However, NAC did not appear to affect the activity of the canonical Wnt signaling pathway. The present findings suggested that the beneficial effects of NAC in autism may be associated with its antioxidative properties, and may not be mediated by the canonical Wnt pathway. However, it may be hypothesized that the canonical Wnt pathway can be indirectly regulated by NAC through the activation of other signaling pathways or upstream factors. Taken together, the present study has contributed to the elucidation of the molecular mechanisms that underlie the actions of NAC in autism, suggesting its potential for the development of novel therapeutic strategies for the treatment of patients with autism.

N-acetylcysteine as an adjuvant therapy for Helicobacter pylori eradication

Background Helicobacter pylori (H pylori) is one of the most common pathogens to establish and cause infection in human beings, affecting about 50% of the world's population. Prevalence may be as high as 83% in Latin American countries and as low as 17% in North America. Approximately 20% of infected people will manifest disease; people at high risk include those who live in low- and middle-income countries with poor sanitary conditions, since the mechanism of transmission seems to be oral-oral or faecal-oral (mostly during infancy). There are several antibiotic regimens to treat the infection, but antibiotic resistance is growing around the world. New adjuvant drugs - such as probiotics, statins, curcumin, and N-acetylcysteine (NAC) - are being tested to enhance eradication rates.N-acetylcysteine can destabilise the biofilm structure; it also has synergic action with antibiotics, and bactericidal effects. In addition, NAC has antioxidant properties, and has a primary mucolytic effect by reducing the thickness of the gastric mucus layer, both of which may exert beneficial adjuvant effects on H pylori eradication. Objectives To assess the efficacy and safety of N-acetylcysteine as an adjuvant therapy to antibiotics for Helicobacter pylori eradication. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to April 2018), Embase (1988 to April 2018), CINAHL (1982 to April 2018), LILACS (1982 to April 2018), grey literature databases and trials registries. We handsearched the reference lists of relevant studies. We screened 726 articles and assessed 18 for eligibility. Selection criteria We included randomised controlled trials (RCTs) of any antibiotic regimen plus NAC, in adults infected with H pylori. To be included, trials had to use a control consisting of the same antibiotic regimen with or without placebo. Outcomes of interest were eradication rates, and gastrointestinal, toxic, and allergic adverse events. Reporting of the primary outcomes listed here was not an inclusion criterion for the review. Data collection and analysis Two review authors independently reviewed and extracted data and completed the 'Risk of bias' assessments. A third review author independently confirmed the 'Risk of bias' assessments. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. Main results We included eight RCTs (with a total of 559 participants) in this review. The studies recruited outpatients aged between 17 and 76 years who were referred to endoscopy centres in several different countries. The certainty of evidence was reduced for most outcomes due to the poor methodological quality of included studies; issues mainly related to the generation of allocation sequence, allocation concealment, and blinding (this last domain related specifically to adverse outcomes).We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates, compared with the addition of placebo or no NAC (38.8% versus 49.1%, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.51 to 1.08; participants = 559; studies = eight; very low-certainty evidence). A post-hoc sensitivity analysis, in which we removed studies that tested antibiotic regimens no longer recommended in clinical practice, showed that the addition of NAC may improve eradication rates compared to control (27.2% versus 37.6%, RR 0.71, 95% CI 0.53 to 0.94; participants = 397; published studies = five).We are uncertain whether NAC is associated with a higher risk of gastrointestinal adverse events compared to control (23.9% versus 18.9%, RR 1.25, 95% CI 0.85 to 1.85; participants = 336; studies = five; very low-certaintyevidence), or allergic adverse events (2% versus 0%, RR 2.98, 95% CI 0.32 to 27.74; participants = 336; studies = five; very low-certainty evidence). There were no reports of toxic adverse events amongst included studies. Authors' conclusions We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates compared with the addition of placebo or no NAC. Due to the clinical, statistical and methodological heterogeneity found in included studies, and the uncertainty observed when analysing therapy subgroups, any possible beneficial effect of NAC should be regarded cautiously.We are uncertain whether NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared with placebo or no NAC. There were no reports of toxic adverse events amongst the included studies.Further large, well-designed, randomised clinical studies should be conducted, with good reporting standards and appropriate collection of efficacy and safety outcomes, especially for current recommended antibiotic regimens.

N-acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma

The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion+NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis.

Protective Effect of Topical Application of α-Tocopherol and/or N-Acetyl Cysteine on Argemone Oil/Alkaloid-Induced Skin Tumorigenesis in Mice

Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.

N -acetyl cysteine in clomiphene citrate resistant polycystic ovary syndrome: A review of reported outcomes

Clomiphene citrate (CC) has been the gold-standard drug for ovulation induction in polycystic ovary syndrome (PCOS), but still CC resistance is seen in approximately 15-40% in women with PCOS. N-acetyl cysteine (NAC), a safe and cheap drug available in the market many years ago as mucolytic agent, was found to have a role in infertility management. Recently, some reports discussed the possible beneficial effects of NAC on ovulation. The biological properties of the NAC make this drug a potential candidate for its use in the infertility treatment, especially in the PCOS in inducing or augmenting ovulation. An updated electronic search was performed through PUBMED, MEDLINE, and COCHRANE and focused on peer-reviewed, full text, randomized controlled trials, and observational cohort or case-control studies for role of NAC in CC-resistant PCOS. Thorough search through all the clinical studies showed mixed results. Studies with positive results showed improvement in induction of ovulation as compared to negative studies showing contrary results. More randomized clinical trials are still needed to establish its definitive role in CC-resistant PCOS.

Subendocardial Increase in Reactive Oxygen Species Production Affects Regional Contractile Function in Ischemic Heart Failure

Heart failure (HF) is characterized by regionalized contractile alterations resulting in loss of the transmural contractile gradient across the left ventricular free wall. We tested whether a regional alteration in mitochondrial oxidative metabolism during HF could affect myofilament function through protein kinase A (PKA) signaling. Twelve weeks after permanent left coronary artery ligation that induced myocardial infarction (MI), subendocardial (Endo) cardiomyocytes had decreased activity of complex I and IV of the mitochondrial electron transport chain and produced twice more superoxide anions than sham Endo and subepicardial cells. This effect was associated with a reduced antioxidant activity of superoxide dismutase and Catalase only in MI Endo cells. The myofilament contractile properties (Ca(2+) sensitivity and maximal tension), evaluated in skinned cardiomyocytes, were also reduced only in MI Endo myocytes. Conversely, in MI rats treated with the antioxidant N-acetylcysteine (NAC) for 4 weeks, the generation of superoxide anions in Endo cardiomyocytes was normalized and the contractile properties of skinned cardiomyocytes restored. This effect was accompanied by improved in vivo contractility. The beneficial effects of NAC were mediated, at least, in part, through reduction of the PKA activity, which was higher in MI myofilaments, particularly, the PKA-mediated hyperphosphorylation of cardiac Troponin I. The Transmural gradient in the mitochondrial content/activity is lost during HF and mediates reactive oxygen species-dependent contractile dysfunction. Regionalized alterations in redox signaling affect the contractile machinery of sub-Endo myocytes through a PKA-dependent pathway that contributes to the loss of the transmural contractile gradient and impairs global contractility.

N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study

Treatment with N-acetylcysteine (NAC) normalizes glutamate (Glu) homeostasis and prevents relapse in drug-dependent animals. However, the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated. Proton magnetic resonance spectroscopy ((1)H MRS) was used to investigate Glu changes in the dorsal anterior cingulate cortex (dACC) after a single dose of NAC in cocaine-dependent patients and normal controls. In an open-label, randomized, crossover study, 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions: one group receiving no compound and the other following a single administration of 2400 mg NAC. The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity. In the medication-free condition, Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls. After administration of NAC, Glu levels were reduced in the cocaine-dependent group, whereas NAC had no effect in healthy controls. Higher baseline Glu levels were associated with higher impulsivity, and both were predictive of greater NAC-induced Glu reduction. The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients. These findings may have important implications for treatment, because abnormal Glu levels are related to relapse, and treatment with NAC prevented relapse in animal studies. Furthermore, clinical studies have indicated beneficial effects of NAC in cocaine-dependent patients, and the current study suggests that these beneficial effects might in part be mediated by the ability of NAC to normalize glutamatergic abnormalities.

Antifibrotic and antioxidant effects of N-acetylcysteine in an experimental cholestatic model

Several studies have suggested that oxidative stress may play an important role in the pathogenesis of hepatic injury during cholestasis in rats and humans. The aim of this study was to evaluate the ability of N-acetylcysteine (NAC) to prevent the damage induced by bile duct ligation (BDL) for 28 days in male Wistar rats. NAC was administered daily (300 mg/kg, orally) for 28 days. Alanine aminotransferase was quantified in the serum; lipid peroxidation, glutathione, and catalase activity were measured in the liver. Fibrosis was assessed by measuring the liver hydroxyproline content; transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-10 were determined in the liver by a western blot and quantified densitometrically. The induction of cholestatic damage by BDL was associated with an increase in alanine aminotransferase. Oxidative stress was also evaluated; lipid peroxidation increased, whereas the liver glutathione content and catalase activity decreased by BDL. NAC treatment prevented these alterations. Hydroxyproline was increased by chronic BDL, but NAC preserved the normal hydroxyproline levels. Cytokines TGF-β, IL-6, and IL-10 increased after 28 days of BDL. NAC was effectively significant in preventing TGF-β and IL-6 expression and further augmented the IL-10 expression. Our data indicate that in the development to cholestatic liver damage, oxidative stress plays an important role and this in turn leads to fibrosis. This study shows that the beneficial effects of NAC are because of its antioxidant and immunomodulatory properties.

Beneficial Effect of N-acetylcysteine on Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Although delusions are a frequent finding in patients with Alzheimer9s disease (AD), their mechanism is not well known. We carried out Tc 99m HMPAO single-photon emission computed tomography studies in 16 AD patients with delusions and 29 AD patients without delusions comparable in age, years of education, duration of illness, and severity of dementia. Although we found no significant between-group differences in performance on neuropsychological tasks, AD patients with delusions had significantly lower mean cerebral blood flow in both the left and right temporal lobes.

Beneficial Effects of N-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague–Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

N-Acetylcysteine attenuates cerebral complications of non-acetaminophen-induced acute liver failure in mice: antioxidant and anti-inflammatory mechanisms

N-acetylcysteine (NAC) is an effective antidote to treat acetaminophen (APAP)-induced acute liver failure (ALF). NAC is hepatoprotective and prevents the neurological complications of ALF, namely hepatic encephalopathy and brain edema. The protective effect of NAC and its mechanisms of action in ALF due to other toxins, however, are still controversial. In the present study, we investigated the effects of NAC in relation to liver pathology, hepatic and cerebral glutathione, plasma ammonia concentrations, progression of encephalopathy, cerebral edema, and plasma proinflammatory cytokines in mice with ALF resulting from azoxymethane (AOM) hepatotoxicity, a well characterized model of toxic liver injury. Male C57BL/6 mice were treated with AOM (100 microg/g; i.p.) or saline and sacrificed at coma stage of encephalopathy in parallel with AOM mice administered NAC (1.2 g/kg; i.p.). AOM administration led to hepatic damage, significant increase in plasma transaminase activity, decreased hepatic glutathione levels and brain GSH/GSSG ratios as well as increased expression of plasma proinflammatory cytokines. NAC treatment of AOM mice led to reduced hepatic damage and improvement in neurological function, normalization of brain and hepatic glutathione levels as well as selective attenuation in expression of plasma proinflammatory cytokines. These findings demonstrate that the beneficial effects of NAC in experimental non-APAP-induced ALF involves both antioxidant and anti-inflammatory mechanisms.

Beneficial Effects of N-Acetyl Cysteine on Pancreas and Kidney Following Experimental Pancreatic Ischemia-Reperfusion in Rats

OBJECTIVE:To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model.METHODS AND MATERIALS:Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion.RESULTS:There were significant differences in amylase levels between Group 1 (6.11±0.55) and Group 2 (10.30±0.50) [p=0.0002] as well as between Group 2 (10.30±0.50) and Group 4 (7.82±0.38) [p=0.003]; creatinine levels between Group 1 (0.52 ± 0.07) and Group 2 (0.77±0.18) [p=0.035] as well as between Group 2 (0.77±0.18) and Group 3 (0.48±0.13) [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27±0.96) and Group 2 (2.60±3.01) [p=0.026] as well as between Group 2 (2.60±3.01) and Group 4 (0.52±0.56) [p=0.002]. A decrease in pancreatic tissue GST-α3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006), and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively).CONCLUSION:This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model.

Cystatin C and Creatinine as Markers for Radiocontrast-Induced Nephropathy in Patients Treated with N-Acetylcysteine

The beneficial effect of N-acetylcysteine (NAC) in the prevention of radiocontrast-induced nephropathy (RCIN) as well as the definition of an adequate surrogate parameter for the evaluation of the incidence of RCIN remain points of controversial discussion. Nearly all clinical studies used an increase in serum creatinine to define renal injury, although cystatin C is suggested to be superior to creatinine in estimating glomerular filtration rate (GFR). Furthermore, a recent study showed that in healthy volunteers, NAC leads to a decrease in serum creatinine without influencing serum cystatin C concentrations, implicating a possible overestimation of the protective effect of NAC on the incidence of RCIN. We compared serum creatinine and cystatin C levels in patients with chronic kidney disease undergoing coronary angiography, as these patients are to be considered at highest risk for the development of RCIN. A total of three doses of NAC was given orally, and patients received isotonic saline intravenously. Serum levels at baseline and 24 hours after angiography were not significantly different for serum creatinine (1.72 ± 0.08 mg/dl and 1.72 ± 0.08 mg/dl) and for cystatin C (1.72 ± 0.09 mg/dl and 1.76 ±0.10 mg/dl). There was a significant positive correlation between creatinine and cystatin C serum levels before and after exposure to radiocontrast medium (p < 0.05) in all patients, including subgroup analyses. We conclude that serum creatinine and cystatin C are equivalent surrogate parameters for the evaluation of NAC in the prevention of RCIN. Furthermore, we present a prophylactic treatment regime easily applicable even in an outpatient setting, which seems to protect very effectively against RCIN in a high-risk group of patients.

N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition

The ability of transforming growth factor-beta1 (TGF-beta1) to induce epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC) in vitro and in vivo, together with the demonstration of EMT in biopsies of idiopathic pulmonary fibrosis (IPF) patients, suggests a role for TGF-beta1-induced EMT in disease pathogenesis. We investigated the effects of N-acetylcysteine (NAC) on TGF-beta1-induced EMT in a rat epithelial cell line (RLE-6TN) and in primary rat alveolar epithelial cells (AEC). RLE-6TN cells exposed to TGF-beta1 for 5 days underwent EMT as evidenced by acquisition of a fibroblast-like morphology, downregulation of the epithelial-specific protein zonula occludens-1, and induction of the mesenchymal-specific proteins alpha-smooth muscle actin (alpha-SMA) and vimentin. These changes were inhibited by NAC, which also prevented Smad3 phosphorylation. Similarly, primary alveolar epithelial type II cells exposed to TGF-beta1 also underwent EMT that was prevented by NAC. TGF-beta1 decreased cellular GSH levels by 50-80%, whereas NAC restored them to approximately 150% of those found in TGF-beta1-treated cells. Treatment with glutathione monoethyl ester similarly prevented an increase in mesenchymal marker expression. Consistent with its role as an antioxidant and cellular redox stabilizer, NAC dramatically reduced intracellular reactive oxygen species production in the presence of TGF-beta1. Finally, inhibition of intracellular ROS generation during TGF-beta1 treatment prevented alveolar EMT, but treatment with H2O2 alone did not induce EMT. We conclude that NAC prevents EMT in AEC in vitro, at least in part through replenishment of intracellular GSH stores and limitation of TGF-beta1-induced intracellular ROS generation. We speculate that beneficial effects of NAC on pulmonary function in IPF may be mediated by inhibitory effects on alveolar EMT.

Effects of N-acetylcysteine on Semen Parameters and Oxidative/Antioxidant Status

To examine whether a beneficial effect of N-acetylcysteine (NAC) on semen parameters and oxidative/antioxidant status in idiopathic male infertility exists. The production of reactive oxygen species is a normal physiologic event in various organs. However, overproduction of reactive oxygen species can be detrimental to sperm and has been associated with male infertility. Our study included 120 patients who had attended our clinic and were diagnosed with idiopathic infertility according to medical history and physical and seminal examination findings, as initial evaluations. The patients were divided randomly into 2 groups. Those in the study group (60 men) were given NAC (600 mg/d orally) for 3 months; the control group (60 men) received a placebo. The oxidative status was determined by measuring the total antioxidant capacity, total peroxide and oxidative stress index in plasma samples. The sperm parameters were evaluated after NAC treatment and were compared with those in the control group. NAC had significant improving effects on the volume, motility, and viscosity of semen. After NAC treatment, the serum total antioxidant capacity was greater and the total peroxide and oxidative stress index were lower in the NAC-treated group compared with the control group. These beneficial effects resulted from reduced reactive oxygen species in the serum and reduced viscosity of the semen. No significant differences were found in the number or morphology of the sperm between the 2 groups. We believe that NAC could improve some semen parameters and the oxidative/antioxidant status in patients with male infertility.

Effect of N-acetylcysteine on Radiation-induced Genotoxicity and Cytotoxicity in Rat Bone Marrow

The aim of this study is to evaluate the potential radioprotective effects of N-acetylcysteine (NAC) against genotoxicity and cytotoxicity. The effect of WR-2721, as a representative of clinically used radioprotector, was compared with that of NAC, using the chromosomal aberration (CA) and micronucleus (MN) test systems in the irradiated rat's femoral bone marrow cells. We also investigated the mitotic index (MI), and the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). The rats (n = 16) were divided randomly and equally into four groups: Control (C), Radiation (R), R+NAC (received irradiation and 1000 mg/kg NAC) and R+WR-2721 (received irradiation and 200 mg/kg WR-2721) rats. All the irradiated groups received whole-body gamma irradiation as a single dose of 6 Gy. Group R showed higher CA and MN formation when compared to C. Group R showed higher frequency of MN formation when compared to both R+NAC and R+WR-2721. The mean MI and PCE/NCE ratios were lower in Group R when compared to those of Group C. The mean MI and PCE/NCE ratios of both R+NAC and R+WR-2721 groups were lower when compared to those of Group C. The MI in Group R was lower when compared to that of both R+NAC and R+WR-2721 groups. In this study, the results give clues about the beneficial effects of NAC against radiation-induced genotoxicity and cytotoxicity in rat bone marrow and its effect may be comparable to that observed for WR-2721.

The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats

The clinical use of cisplatin (cis-diamminedichloro-platinum II, CDDP) is highly limited by its nephrotoxicity. Although N-acetylcysteine (NAC), a thiol-containing antioxidant, has been documented to be effective in attenuating renal injury induced by CDDP, the precise mechanisms involved in its renoprotection have not been completely clarified. We investigated the effects of NAC on oxidative stress and oxidation-associated signals, such as p38 mitogen-activated protein kinase (MAPK), NF-kappaB and TNF-alpha, in CDDP-induced acute renal failure (ARF) rats, in comparison to the effects of melatonin (MT), one of the physiological TNF-alpha inhibitors, and pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor. NAC blocked oxidative stress, p38 MAPK activation, caspase-3 cleavage, tissue apoptosis, renal dysfunction and morphological damage induced by CDDP. CDDP-triggered NF-kappaB translocation into the nucleus and TNF-alpha mRNA increase in the kidney were also inhibited in NAC-treated rats. MT downregulated the TNF-alpha mRNA level, and PDTC inhibited the increases in both NF-kappaB translocation and TNF-alpha mRNA. Neither MT nor PDTC were capable of interfering with oxidative stress, p38 MAPK phosphorylation, caspase-3 cleavage, tissue apoptosis and kidney injury induced by CDDP. These data suggest that oxidative stress and p38 MAPK-mediated apoptotic cell death pathways are involved, at least in part, in the pathogenesis of CDDP-induced ARF, and negative regulation of p38 MAPK activation through inhibition of oxidative stress appears to play a central role in the beneficial effects of NAC.

Comparison of the Protective Effect of N-Acetylcysteine by Different Treatments on Rat Myocardial Ischemia-Reperfusion Injury

Reactive oxygen species have been known as important contributors to ischemia /reperfusion (I/R) injury. Studies on the beneficial effect of N-acetylcysteine (NAC), a potent antioxidant, on limiting infarct size induced by I/R yielded contrasting results. The present study was undertaken to compare the effect of NAC by different administration methods on infarct size in a rat myocardial I/R model. Rats underwent 30 min of left coronary occlusion followed by 4 h of reperfusion. Treatment with continuous infusion of NAC (150 mg/kg per hour) from 30 min before occlusion for 2 h (until 1 h after the start of reperfusion) produced a significant limitation of the infarct size as a percentage of the ischemic area (8%) compared to the non-treated control (60%). However, bolus injection of 150 mg/kg at 30 min prior to occlusion and 5 min prior to reperfusion failed to reduce it (56%) although the total dose is the same. The decreased total glutathione content and glutathione peroxidase activity in the ischemic region were recovered in the continuous infusion group, but not in the bolus injection group. The increased myeloperoxidase activity and phosphorylation of inhibitor κ B after I/R were inhibited by the continuous treatment. These results indicate that the protective effect of NAC on myocardial infarction induced by I/R was different depending on the administration method. It is necessary to maintain blood concentration during the early period of reperfusion to obtain the beneficial effect of NAC.

The Beneficial Effect of N-Acetylcysteine and Ciprofloxacin Therapy on the Outcome of Ischemic Fulminant Hepatic Failure

The Beneficial Effect of N-Acetylcysteine and Ciprofloxacin Therapy on the Outcome of Ischemic Fulminant Hepatic Failure

Beneficial Effect of N-Acetylcysteine against Organophosphate Toxicity in Mice

Recent studies showed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compounds toxicity. The aim of present study was to investigate either prophylactic and therapeutic effects of N-acetylcysteine (NAC) against fenthion-induced oxidative stress in mice. Additionally, the effects on survival rates were investigated. Therefore, we determined the changes of the blood levels of glutathione (GSH), malondialdehyde (MDA), nitrite, and nitrate in blood or serum. Additionally, all animals were observed for 6 h and the survival rates were recorded. It was found that fenthion administration increased the levels of MDA, and decreased the levels of GSH, nitrite and nitrate. On the other hand, both prophylactic and therapeutic NAC treatment decreased the levels of MDA, and increased the levels of GSH, nitrite, and nitrate. The results showed that NAC is able to attenuate the fenthion-induced oxidative stress whereby NAC has not only prophylactic but also therapeutic activity in fenthion poisoning. On the other hand, we found that NAC can clearly improve survival rates in mice administered with an acute high dose of fenthion poisoning. In conclusion, NAC can decrease OP-induced oxidative stress and mortality rate, but the exact mechanism of its NAC protective effect needs to be explored further.