NAC-treated Group Research Articles

Effects of dietary supplementation with N-acetyl cysteine on antioxidant capacities and the expression of inflammatory cytokines in weaned piglets

The present study was conducted to investigate the effects of N-acetylcysteine (NAC) on antioxidant capacities and the expression of inflammatory cytokines in weaned piglets. In total, 15 litters, containing 150 14-day-old piglets, were divided, by litter, into suckling (control), weaning and NAC groups. Thus, there were five litters per group. Compared with the suckling group, the weaning group had increased (p < .05) malondialdehyde (MDA), nitric oxide (NO), hydrogen peroxide (H2O2) and interleukin (IL)-6 contents in their serum and pro-inflammatory cytokine IL-6 and IL-1β expression levels in the jejunum, while they had decreased superoxide dismutase (SOD) (p = .055) and glutathione peroxidase (GSH-Px) (p = .057) activities, as well as IL-4 (p < .05) concentrations in their serum and I-κBα expression (p < .05) in their jejunum. Dietary supplementation with NAC had improved (p < .05) antioxidant status in serum and increased (p < .05) levels of IL-4 but decreased (p < .05) mRNA expression levels and concentrations of IL-6 and IL-1β. Meanwhile, the I-κBα expression level in the jejunum of the NAC-treated group increased (p < .05) compared with the weaning group. In conclusion, weaning resulted in oxidative stress, and dietary supplementation with NAC could increase the antioxidant capacities, while decreasing the jejunal expression of inflammatory cytokines in weaned piglets.

Alcohol use during a trial of N-acetylcysteine for adolescent marijuana cessation

AimsCurrent adolescent alcohol treatments have modest effects and high relapse rates. Evaluation of novel pharmacotherapy treatment is warranted. N-acetylcysteine (NAC), an over-the-counter antioxidant supplement with glutamatergic properties, is a promising treatment for marijuana cessation in adolescents; however, its effects on adolescent drinking have not been examined. To that end, this secondary analysis evaluated: (1) the effect of NAC vs. placebo on alcohol use over an eight-week adolescent marijuana cessation trial and (2) the role of marijuana cessation and reduction on subsequent alcohol use. MethodsMarijuana-dependent adolescents (ages 15–21; N=116) interested in treatment were randomized to NAC 1200mg or matched placebo twice daily for eightweeks. Participants were not required to be alcohol users or interested in alcohol cessation to qualify. ResultsThere were no demographic or baseline alcohol use differences between participants randomized to NAC vs. placebo (ps>0.05). Of the 89 participants returning for ≥one visit following randomization, 77 reported ≥one alcoholic drink in the 30days prior to study entry and averaged 1.3 (SD=1.4) binge drinking days per week. During treatment, less marijuana use (measured via urine cannabinoid levels) was associated with less alcohol use in the NAC-treated group but not in the placebo-treated group (p=0.016). ConclusionsThere was no evidence of compensatory alcohol use during marijuana treatment. In fact, in the NAC group, lower levels of marijuana use were associated with less alcohol use, suggesting NAC effects may generalize to other substances and could be useful in decreasing adolescent alcohol use. NAC trials specifically focused on alcohol-using adolescents are warranted.

N-Acetylcysteine Ameliorates Experimental Autoimmune Myocarditis in Rats via Nitric Oxide.

Oxidative stress may play an important role in the development of myocarditis. We investigated the effects of N-acetylcysteine (NAC), a potent antioxidant, on experimental autoimmune myocarditis (EAM) in rats. A rat model of porcine myosin-induced EAM was used. After the immunization with myosin, NAC (20 mg/kg/d) or saline was injected intraperitoneally on days 1 to 21. Additional myosin-immunized rats treated with NAC were orally given 25 mg/kg/d of N(G)-nitro-l-arginine methylester (l-NAME), an inhibitor of nitric oxide (NO) synthase, and N(G)-nitro-d-arginine methylester (d-NAME), an inactive enantiomer. The NAC treatment improved cardiac pathology associated with reduced superoxide production. In the EAM rats treated with NAC associated with oral l-NAME, but not with oral d-NAME, the severity of myocarditis was not reduced. Expression of intercellular adhesion molecule 1 was reduced by NAC treatment. Myocardial c-kit(+) cells were demonstrated only in the NAC-treated group. Hemodynamic study showed that the increased left ventricular mass produced by myocardial inflammation tended to be reduced by NAC treatment. Treatment with NAC ameliorated myocardial injury via NO system in a rat model of myocarditis.

Overdose with modified-release paracetamol (Panadol Osteo®) presenting to a metropolitan emergency medicine network: a case series.

There are currently no large cases series documenting poisoning with paracetamol modified-release (Panadol Osteo®, GlaxoSmithKline, Sydney, NSW, Australia). Management guidelines recommend at least two serum paracetamol concentrations 4 h apart and initiating treatment with N-acetylcysteine (NAC) if more than 10 g is ingested. To describe a cohort of Panadol Osteo® poisoning and determine if the management of identified cases was consistent with existing guidelines. Descriptive retrospective case series presenting to a metropolitan hospital network with paracetamol poisoning from October 2009 to September 2013. There were 42 cases of Panadol Osteo® poisoning identified. Twenty-nine patients (median ingested dose 19 950 mg) were treated with NAC, of which 27 were acute single ingestions. Of NAC-treated patients, 85% (23/27) had an initial serum paracetamol concentration that was above the nomogram line. However, 15% (4/27) had an initial non-toxic concentration that later increased above the line. In 14 untreated patients (median ingested dose 7980 mg), one was an unrecognised late line-crosser with initial non-toxic serum paracetamol concentration. Only 43% (6/14) had a repeat paracetamol concentration measured. Three patients had a 4 h paracetamol >500 μmol/L. Late line-crossing was seen in the NAC-treated group at this level. In two untreated patients, NAC should have been commenced on the reported dose. Most patients presenting with Panadol Osteo® poisoning requiring NAC treatment had an initial serum paracetamol concentration indicating need for treatment. A small number of late treatment nomogram line-crossers was seen on repeat paracetamol estimation. The current guideline for Panadol Osteo® poisoning would have detected all cases requiring NAC treatment.

The effects of erdosteine and N-acetylcysteine on apoptotic and antiapoptotic markers in pulmonary epithelial cells in sepsis.

This study investigated the frequency of apoptosis in rat pulmonary epithelial cells after the injection of an intraperitoneal endotoxin lipopolysaccharide (LPS), the effects of LPS on apoptotic (bax, caspase-3) and antiapoptotic (bcl-2) markers during lung damage, and the protective effects of two known antioxidant agents, erdosteine and N-acetylcysteine (NAC). Male Wistar rats were divided into the following six groups, which included nine rats each: two control groups, two LPS-treated groups, one erdosteine-treated group (150 mg/kg), and one NAC-treated group (150 mg/kg). LPS was injected intraperitoneally at a dosage of 20 mg/kg. Following LPS injection, the antioxidants were orally administered. The rats were sacrificed at 24 h after LPS administration. The levels of apoptosis in bronchiolar and alveolar cells were determined using the TUNEL-staining method. Immunohistochemical staining of cytoplasmic bax, caspase-3, and bcl-2 in the epithelial cells was performed. Erdosteine and NAC significantly reduced the rate of LPS-induced pulmonary epithelial cell apoptosis. The effect of NAC on regulating apoptosis was weaker than that of erdosteine. Erdosteine and NAC significantly reduced the local induction of bax and caspase 3 and significantly increased the reduced local production of bcl-2. These findings suggest that erdosteine and NΑC can effectively protect the lungs from the damaging effects of LPS.

N-Acetylcysteine Improves Pancreatic Microcirculation and Alleviates the Severity of Acute Necrotizing Pancreatitis

Background/AimsTo investigate the beneficial effect of N-Acetylcysteine (NAC) on pancreatic microvascular perfusion in acute necrotizing pancreatitis (ANP).MethodsFifty-four rats were divided into a control group, an ANP group and an NAC-treated group. The ANP model was established by a retrograde injection of 3% sodium taurocholate into the pancreatic duct. The NAC-treated group received an intravenous infusion of NAC just 2 hours before and 30 minutes after the induction of ANP. The pancreatic microvascular perfusion was measured with laser Doppler flowmetry and pancreatic samples were collected for histological examination.ResultsThe microvascular perfusion in the NAC-treated group decreased slightly and exhibited a significant increase compared to the ANP group (p<0.01). A pathological examination revealed that edema and inflammatory infiltration decreased, and the hemorrhaging and necrosis of the pancreas were significantly reduced.ConclusionsNAC could improve pancreatic microvascular perfusion and alleviate the severity of sodium taurocholate-induced ANP, possibly representing a new therapeutic approach to prevent the progression of ANP.

N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine

Context. Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. Objective. Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. Materials and methods. Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 μg.kg− 1, 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml− 1 Mucomyst™ at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. Results. Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO2) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO2) significantly increased, and arterial blood pH and bicarbonate (HCO3−) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO3− levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. Discussion. NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving clinically relevant physiological indices affected by sulfur mustard exposure. Conclusion. Beneficial effects of nebulized NAC were apparent following inhaled sulfur mustard exposure. Further therapeutic benefit may result from a combination therapy approach.

In Vitro N-Acetyl-l-Cysteine Promotes Proliferation and Suppresses Interleukin-8 Expression in Adipose-Derived Stem Cells

Adipose-derived stem cells (ADSCs) hold great promise for repair and regeneration of burn wounds by producing growth factors, but proinflammatory cytokines such as interleukin-8 (IL-8) released by ADSCs would potentially deepen the wound and inhibit healing. The reported research aimed to identify the effects of N-acetyl-L-cysteine (NAC) on the proliferation, death, and IL-8 production of ADSCs. In the presence or absence of NAC, ADSC proliferation was examined using a CCK-8 Kit, and cell death was evaluated by flow cytometry analysis. Subsequently, IL-8 mRNA expression was detected by reverse transcriptase-polymerase chain reaction and protein production by enzyme-linked immunoassay. Findings showed that cell proliferation in the NAC-treated group was a significant 1.53-fold greater than in the control group, that the apoptosis rate of ADSCs decreased by 55.4 % compared with the control group, and that the necrosis rate decreased by 48.8 %. Additionally, the IL-8 mRNA expression decreased to 46.2 ± 8.7 % that of the control group, and the IL-8 protein production decreased to 9.98 ± 0.57 %. The authors believe that NAC might be helpful in burn wound repair and regeneration by stimulating the proliferation of ADSCs, inhibiting cell death, and suppressing IL-8 production. This journal requires that authors assign a level of evidence to each article.

Cavity Margin Status Is an Independent Risk Factor for Local-Regional Recurrence in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy Before Breast-Conserving Surgery

The objection of this study is to investigate whether the cavity margin (CM) status has different predictive efficacy for local-regional recurrence (LRR) in patients who have received or have not received neoadjuvant chemotherapy (NAC) before breast-conserving surgery. We identified 61 patients who received NAC before breast-conserving surgery. A nonrandomized unmatched cohort of 295 patients without history of receiving NAC were also included in this study. Clinicopathological features and follow-up data were abstracted and analyzed. Patients in the NAC-treated group had more advanced diseases when compared with patients in the nonNAC-treated group. With a median follow-up of 42 months, the LRR-free survival rate of patients with positive CMs was significantly lower than that of patients with negative CMs in the NAC-treated group. This distinction was not observed in the nonNAC-treated group. Univariate and multivariate analysis revealed that positive CM was the only independent predictive factor for LRR in the NAC-treated group but not in nonNAC-treated patients. CM status had different predictive efficacy for LRR in different settings. Association between CM status and LRR was observed in NAC-treated patients rather than nonNAC-treated patients. More extensive surgical treatment might be needed in NAC-treated patients when their CMs are positive.

Intraoperative pH Values After N-acetylcysteine Administration During Liver Transplantation

We investigated whether intraoperative administration of N-acetylcysteine (NAC) to liver transplant recipients affected pH values. This prospective, randomized, double-blind clinical trial included liver transplant recipients who were randomly assigned to NAC-treated (n = 25) or placebo (n = 25) groups. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose during the next 24 hours. The placebo group received equal amounts of 5% dextrose solution during the same times. Peripheral blood samples were drawn in Ca 2+-80 IU–containing syringes after induction of anesthesia (I-1), at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo, at 5 minutes before reperfusion (I-3), at 5 minutes after reperfusion (I-4), at 20 minutes after reperfusion (I-5), at 60 minutes after reperfusion (I-6), and at 1 hour after completion of the procedure (I-7). pH levels, which were determined using a radiometer ABL77 (Copenhagen, Denmark), were significantly lower among the NAC than the placebo group at I-4 ( P = .027) and I-5 ( P = .031). An early decrease in pH values was detected in the NAC-treated group at 5 minutes before reperfusion (I-3; P = .051). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly decreased recipient pH values at 5 and 20 minutes after reperfusion, a decrease that was detected at 5 minutes before reperfusion (I-3). The decrease seemed to be associated with NAC metabolism.

Efficacy of TopicalN-Acetylcysteine in the Treatment of Meibomian Gland Dysfunction

To evaluate the efficacy of topical N-acetyl-cysteine (NAC) therapy in patients with meibomian gland dysfunction (MGD). Twenty patients with MGD were prospectively randomized and assigned into 2 groups. The patients were instructed to use either NAC 5% or preservative-free artificial tear topically 4 times a day for a month. All patients were instructed to apply lid hygiene once daily. Preservative-free artificial tears treated group served as control. Paired sample Student's t-tests were used to detect differences between the baseline and 1 month after treatment initiation in mean ocular symptoms, fluorescein break-up time (FBUT) values, and Schirmer scores in each group. Difference in mean ocular symptoms, Schirmer's test scores, and FBUT values between the baseline and 1 month after treatment initiation were compared between the groups using Mann-Whitney U test. One month of topical NAC therapy provided statistically significant improvements in FBUT and Schirmer scores as compared with the initial study visit. The average Schirmer increase rate was significantly better in the NAC group than in the control group. Significant improvements for the symptoms of ocular burning, foreign body sensation, and intermittent filmy or blurred vision were noted in both groups; and only NAC-treated group showed improvement for the symptom of itching, at 1 month as compared with 1 day. NAC provided significantly better improvement in itching symptom when compared with controls. Topical administration of NAC is thought to be effective and well tolerated in patients with MGD.

N-acetylcysteine attenuates glycerol-induced acute kidney injury by regulating MAPKs and Bcl-2 family proteins

Rhabdomyolysis-induced acute kidney injury (AKI) accounts for about 10 to 40% of all cases of AKI. It is known that N-acetylcysteine (NAC) is effective in various experimental renal injury models; however, little information is available about the rat model of glycerol-induced rhabdomyolysis. In this study, we hypothesize that NAC plays a renoprotective role via the anti-apoptotic pathway. Male Sprague-Dawley rats were divided into four groups: (i) saline control group, (ii) NAC-treated group (N-acetylcysteine) (150 mg/kg), (iii) glycerol-treated group (50%, 8 ml/kg, IM) and (iv) NAC plus glycerol-treated group. Rats were sacrificed at 24 h after glycerol injection, and the blood and renal tissues were harvested. Glycerol administration caused severe renal dysfunction, which included marked renal oxidative stress, significantly increased blood urea nitrogen (BUN) and serum creatinine levels. Histopathological findings, such as cast formation and tubular necrosis, confirmed renal impairment. We noted a marked activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p-38, in the glycerol-treated group. We also observed high expression of Bax and Bad but only weak expression of Bcl-2 and Bcl-xL in the glycerol-treated group. However, NAC pretreatment significantly improved renal function and decreased the activation of ERK, JNK, Bax and Bad, whereas it increased Bcl-2 and Bcl-xL. These results demonstrate that NAC protects against renal dysfunction, morphological damage and biochemical changes via the anti-apoptotic pathway in the glycerol-induced rhabdomyolysis model in rats.

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.

Oral N‐acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking‐induced COPD in rats

The role of apoptosis in lung destruction in emphysema/COPD is increasingly being recognized. The relationship between anti-oxidants and alveolar septal cell apoptosis in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of the anti-oxidant, N-acetylcysteine (NAC), on the development of emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats. Sprague-Dawley rats (n = 48) were randomly assigned to normal, COPD, sham and NAC groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) in BAL fluid by ELISA, VEGF and VEGF receptor-2 (VEGFR2) protein expression by western blotting, and the apoptotic index (AI) of alveolar septal cells by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. Histopathological evaluations (mean linear intercept (MLI), destructive index (DI)) and lung function measurements were performed. FEV(0.3)/FVC and PEF were lower in the COPD group than in the normal group. MLI and DI were lower in the NAC-treated group than in the COPD or sham-treated groups. As confirmed by western blotting, the levels of VEGF in BAL fluid were higher in the NAC-treated group than in the COPD group. VEGFR2 protein expression was higher in the NAC-treated group than in the COPD group. The AI was significantly lower in the NAC-treated group than in the COPD group. There was an inverse correlation between levels of VEGF in BAL fluid and the AI of alveolar septal cells. NAC attenuates lung damage, pulmonary emphysema and alveolar septal cell apoptosis by partly reversing the decrease in VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

Effect of N-Acetylcysteine Administration on Intraoperative Plasma Levels of Interleukin-4 and Interleukin-10 in Liver Transplant Recipients

We investigated whether intraoperative administration of N-acetylcysteine (NAC) in liver transplant recipients ameliorated their inflammatory responses by increasing intraoperative plasma levels of interleukin (IL)-4 and IL-10. This prospective, randomized, double-blind clinical trial included liver transplant recipients randomly assigned to the NAC-treated (n = 25) or the placebo (n = 25) group. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose over the next 24 hours, whereas the placebo group received equal amounts of 5% dextrose solution during the same time. Peripheral blood samples were drawn in EDTA-containing tubes after induction of anesthesia (I-1); at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo; at 5 minutes before reperfusion (I-3); at 10 minutes after reperfusion (I-4); at 20 minutes after reperfusion (I-5); at 60 minutes after reperfusion (I-6); and at 1 hour after completion of the liver transplantation (I-7). Cytokine levels were determined using a technique which combined enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Plasma IL-4 levels were significantly higher among the NAC-treated group than the placebo group at I-3 ( P = .046) and I-4 ( P = .041). Plasma IL-10 levels showed significant enhancement in the NAC-treated group at 5 minutes before reperfusion (I-3; P = .007). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly increased recipient IL-4 plasma levels before and after reperfusion, and IL-10 plasma values before reperfusion (I-3). These enhancements seemed to be associated with a protective effect against reperfusion injury.

The effects of erdosteine, N‐acetylcysteine, and vitamin E on nicotine‐induced apoptosis of hippocampal neural cells

This study investigated the frequency of apoptosis in rat hippocampal neural cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha) in nicotine-induced brain damage and the protective effects of three known antioxidant agents, N-acetylcysteine (NAC), erdosteine, and vitamin E. Female Wistar rats were divided into seven groups, each composed of nine rats: 2 negative control groups, 2 positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Apoptosis level in hippocampal neural cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling) method. Staining of cytoplasmic TNF-alpha in hippocampal neural cells and hippocampus MPO activity were evaluated by immunohistochemistry. Nicotine administration had no effect on local TNF-alpha production, or hippocampal MPO activity. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced hippocampal neural cell apoptosis. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced hippocampal neural cell apoptosis.

Regulation of nicotine-induced apoptosis of pulmonary artery endothelial cells by treatment of N-acetylcysteine and vitamin E

This study investigated the frequency of apoptosis in rat pulmonary artery endothelial cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO), tumour necrosis factor alpha (TNF-alpha), and vascular endothelial growth factor (VEGF) in nicotine-induced vascular damage and the protective effects of two known antioxidant agents, N-acetylcysteine (NAC) and vitamin E. Female Wistar rats were divided into four groups, each composed of nine rats: negative control group, positive control group, NAC-treated group (500 mg/kg), and vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. Apoptosis level in endothelial cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling) method. Staining of cytoplasmic TNF-alpha and VEGF in endothelial cells, and perivascular MPO activity were evaluated by immunohistochemistry. The treatments with NAC and vitamin E significantly reduced the rate of nicotine-induced endothelial cell apoptosis. NAC and vitamin E significantly reduced the increases in the local production of TNF-alpha and VEGF, and perivascular MPO activity. This findings suggest that NAC can be as effective as vitamin E in protecting against nicotine-induced endothelial cell apoptosis.

The effects of erdosteine, N‐acetylcysteine and vitamin E on nicotine‐induced apoptosis of cardiac cells

This study was conducted to investigate the frequency of apoptosis in rat cardiomyocytes after intratraperitoneal nicotine injection, in order to examine the roles of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha)] in nicotine-induced cardiac damage and to determine the protective effects of three known antioxidant agents (N-acetylcysteine (NAC), erdosteine and vitamin E) on nicotine toxicity in the heart. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg kg(-1)), one NAC-treated group (500 mg kg(-1)) and one vitamin E-treated group (500 mg kg(-1)). Nicotine was intraperitoneally injected at a dosage of 0.6 mg kg(-1) for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Heart tissue samples were stained with hematoxylin-eosin for histopathological assessments. Apoptosis level in cardiomyocytes was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-alpha in cardiomyocytes and heart MPO activity were evaluated by immunohistochemistry. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced cardiomyocyte apoptosis. The effect of vitamin E on apoptosis regulation was weaker than the effects of erdosteine and NAC. Erdosteine, NAC and vitamin E significantly reduced the increases in the local production of TNF-alpha and heart MPO activity. This findings suggest that the effects of erdosteine and NAC on apoptosis regulation are stronger than that of vitamin E.

Regulation of sepsis-induced apoptosis of pulmonary cells by posttreatment of erdosteine and N-aceylcysteine

This study investigated the frequency of apoptosis in rat pulmonary epithelial cells after intraperitoneal endotoxin (LPS) injection, the effects of LPS on inflammatory markers [myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF)] in lung damage and the protective effects of two known antioxidant agents, erdosteine and N-acetylcysteine (NAC). Male Wistar rats were divided into six groups, each composed of nine rats: two control groups, two LPS-treated groups, one erdosteine-treated group (150 mg/kg), and one NAC-treated group. LPS was intraperitoneally injected at a dosage of 20 mg/kg. Following LPS injection, the antioxidants were administered orally. The rats were killed 24 h after LPS administration. Lung tissue samples were stained with hematoxylin–eosin (H&E) for histopathological assessments. Apoptosis level in epithelial cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-α in epithelial cells and VEGF in endothelial cells, and epithelial MPO activity were evaluated by immunohistochemistry. Posttreatment with erdosteine and NAC significantly reduced the rate of LPS-induced epithelial cell apoptosis. Posttreatment with erdosteine and NAC significantly reduced the increases in the local production of TNF-α and VEGF, and epithelial MPO activity. The effects of NAC on apoptosis, the increases in the local production of TNF-α and VEGF, were weaker than the effects of erdosteine. This finding suggests that the effects of erdosteine at the administered dose on apoptosis regulation are stronger than that of NAC.

The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of pulmonary cells

This study was conducted to investigate the frequency of apoptosis in the pulmonary epithelial cells of rats after intratraperitoneal nicotine injection, in order to examine the role of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α)] in nicotine-induced lung damage, and to determine the protective effects of three known antioxidant agents [ N-acetylcysteine (NAC), erdosteine, and vitamin E] on the lung toxicity of nicotine in the lungs. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was injected intraperitoneally at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally, treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin–eosin (H&E) for histopathological assessments. The apoptosis level in the lung bronchiolar and alveolar epithelium was determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. Cytoplasmic TNF-α in the bronchiolar and alveolar epithelial cells and the lung MPO activity were evaluated immunohistochemically. The protective effect of vitamin E on lung histology was stronger than that of erdosteine or NAC. Treatment with erdosteine, NAC, and vitamin E significantly reduced the rate of nicotine-induced pulmonary epithelial cell apoptosis, and there were no significant differences in apoptosis among the three antioxidants groups. Erdosteine, NAC, and vitamin E significantly reduced the increases in TNF-α staining and lung MPO activity. The effects of erdosteine on the increases in the local TNF-α level and lung MPO activity were weaker than that of NAC or vitamin E. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced pulmonary cell apoptosis.