Effect of N-Acetylcysteine Combined with Lung Rehabilitation Therapy on Exercise Endurance and Quality of Life of Patients with Rheumatoid Arthritis-Related Interstitial Lung Disease

Objective:To explore the effect of N-acetylcysteine combined with lung rehabilitation therapy on exercise endurance and quality of life in patients with rheumatoid arthritis-related interstitial lung disease(RA-ILD).Methods:Fifty-six patients with RA-ILD admitted to Xijing Hospital from May 2022 to January 2024 were randomly divided into two groups:a non-rehabilitation group and a pulmonary rehabilitation group,with 28 patients in each group.Both groups received routine treatment.Additionally,the non-rehabilitation group received N-acetylcysteine treatment,while the lung rehabilitation group received lung rehabilitation treatment in addition to N-acetylcysteine.The improvement in exercise endurance and dyspnea between the two groups after treatment was compared and the quality of life of the patients was observed.Results:After treatment,the exercise endurance score in the lung rehabilitation group(335.67±45.29)was higher than that in the non-rehabilitation group(P<0.05).The dyspnea score in the lung rehabilitation group(0.72±0.16)was lower than that in the non-rehabilitation group(P<0.05).Additionally,FVC(3.18±0.58 L),FEV1(2.28±0.56 L),FEV1/FVC(69.69±5.56),and DLCO(60.53±5.92 mL/mmHg/min)were higher in the lung rehabilitation group compared to the non-rehabilitation group after treatment(P<0.05).Conclusion:Lung rehabilitation therapy combined with N-acetylcysteine treatment can effectively improve dyspnea symptoms,lung function,and exercise endurance in patients with RA-ILD.This approach helps to improve patient’s quality of life and is beneficial for their prognosis.

N-acetylcysteine and reduced glutathione reverse flupirtine-induced liver injury and pro⁃duce other beneficial effects in combination with flupirtine

OBJECTIVE To assess whether N-acetylcysteine(NAC)and reduced glutathione(GSH)are effective in reversing flupirtine-induced hepatotoxicity and whether they have other beneficial effects when combined with flupirtine.METHODS The analgesic effects of NAC and flupirtine were first evaluated in carrageenaninduced inflammatory pain and paclitaxel-induced neuropathic pain.The combination subthreshold⁃ing approach was then used to determine whether the combination of NAC and flupirtine produced synergistic analgesic effects.Hepatotoxicity markers and histopathological examination of the liver were used to assess the efficacy of NAC and GSH in reversing flupirtine-induced hepato⁃toxicity.Finally,the effect of GSH on the safe range of flupirtine was assessed in an acute tox⁃icity assay.RESULTS Flupirtine and NAC pro⁃duced dose-dependent antiallodynic effects evoked by carrageenan and paclitaxel in mice.In the above model,the combination of NAC and flupirtine produced an unexpected synergistic analgesic effect.There were no significant differ⁃ences observed in the hepatotoxicity markers and liver histopathology between the experimen⁃tal group and the control group under NAC and GSH treatment.Finally,GSH(200 mg·kg^(-1))expanded the therapeutic index of flupirtine by 1.77 times.CONCLUSION NAC and GSH are effective in preventing liver damage caused by long-term flupirtine use,which provides a solu⁃tion for the safe and effective treatment of chronic pain with flupirtine.In addition,the other benefi⁃cial effects of NAC and GSH when combined with flupirtine may provide the basis for the devel⁃opment of a new therapy with minimal sideeffects and good efficacy.

Effects of N-acetylcysteine on growth,viability and reactive oxygen species levels in small antral follicles cultured in vitro

Objective:To investigate the effects of different concentrations of N-acetylcysteine on follicular growth and morphology,as well as on viability,levels of reactive oxygen species(ROS)and meiotic progression of oocytes from in vitro cultured bovine early antral follicles.Methods:Isolated early antral follicles(about 500μm)were cultured in TCM-199+alone or supplemented with 1.0,5.0 or 25.0 mM N-acetylcysteine at 38.5℃with 5%CO_(2) for 8 days.Follicle diameters were evaluated at day 0,4 and 8 of culture.At the end of culture,the levels of ROS,chromatin configuration and viability(calcein-AM and ethidium homodimer-1 staining)were investigated in the cumulus-oocyte complexes.Comparisons of follicle diameters between treatments were performed.Data on percentages of morphologically normal follicles,growth rates and chromatin configuration in different treatments were compared.Results:An increase in follicular diameters after culture in all treatments was observed,except for follicles cultured with 25.0 mM N-acetylcysteine.Fluorescence microscopy showed that oocytes cultured in all treatments were stained positively with calcein AM,and that 5.0 mM N-acetylcysteine reduced fluorescence for ethidium homodimer-1.Intracellular levels of ROS in oocytes from follicles cultured with 1.0 mM N-acetylcysteine showed a significant reduction compared to other treatments.The presence of N-acetylcysteine in culture medium did not influence the rates of oocyte at the germinal vesicle stage.Conclusions:N-acetylcysteine at concentrations of 1.0 and 5.0 mM reduces ROS levels and staining for ethidium homodimer-1 in in vitro cultured follicles,respectively,while 25.0 mM N-acetylcysteine decreases follicular growth and the percentages of continuously growing follicles.

Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and Inflammatory Responses in Rats with PM2.5 Induced Lung Injuries

Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: An endoscopist-blinded, prospective, randomized study

AIM： To assess the efficacy of premedicaton with pronase or N-acetylcysteine （NAC） at 20 min before upper gastrointestinal （UGI） endoscopy and to determine whether pronase or NAC pretreatment influences the reliability of the rapid urease test. METHODS： A total of 146 patients were prospectively and randomly assigned into the study groups according to different premedications before endoscopy. One endoscopist assessed mucosal visibility （MV） with scores ranged from 1 to 4 at four sites in the stomach. The sum of the MV scores from these four locations was defined as the total mucosal visibility （TMV） score. Identification of Hpylori was performed using CLO test, histology, and serology. RESULTS： The Group with pronase premedication had a significantly lower TMV score than did the groups with gascon and gascon water （P 〈 0.001 and P 〈 0.01, respectively）. The group with NAC had a significantly lower TMV score than the group with gascon （P 〈 0.01） and a trend of a lower MV score than the group with gascon water （P = 0.06）. The THV score did not significantly differ between the group with pronase and the group with NAC （P = 0.39 and P = 0.14, respectively）. The sensitivity and specifidty of the CLO test were 92.5% and 93.9%, respectively, in groups premedicated with pronase and NAC together.CONCLUSION： Premedication with pronase or NAC at 20 min before UGI endoscopy improves the mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious interference with the CLO test for the identification of H pylori infection.

Efficacy of premedication with activated Dimethicone or N-acetylcysteine in improving visibility during upper endoscopy

AIM:To assess the efficacy of N-acetylcysteine(NAC) and activated Dimethicone in improving endoscopic mucosal visibility.METHODS:A total of 148 patients were randomly allocated into four groups to receive one of the following premedications:group A:100 mL water alone;group B:activated Dimethicone plus water(up to 100 mL);group C:NAC plus water(up to 100 mL);and group D:activated Dimethicone and NAC plus water(up to 100 mL).A single endoscopist blinded to the patients group assessed the gastric mucosal visibility scores(range 1-4) at four sites.The sum of the scores from the four sites was considered as the total mucosal visibility score(TMVS).RESULTS:The patients in group B showed a significantly lower TMVS than those of groups A and C(P < 0.001).The TMVS in patients of group D was significantly lower than that of groups A and C(P < 0.001).The TMVS did not significantly differ between groups B and D(P > 0.05).The difference between TMVS of groups C and A was not significant(P > 0.05).CONCLUSION:Premedication with activated Dimethicone 20 min prior to the upper endoscopy leads to the best visibility.NAC does not improve visualization by itself.

N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes

Cadmium （Cd） is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum （ER） stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine （NAC）, an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 （2.0 mg kg^-1）. As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling （TUNEL）. However, the administration of NAC alleviated Cd-induced germ ceil apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 （GRP78）, an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2a （elF2a）, a downstream target of the double-stranded RNA-activated kinase-like ER kinase （PERK） pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein （XBP）-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response （UPR）. Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein （CHOP） and phosphorylation of c-Jun N-terminal kinase （.INK）, two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.

N-acetylcysteine attenuates reactive-oxygen-speciesmediated endoplasmic reticulum stress during liver ischemia-reperfusion injury

AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).

N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice

BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05). The levels of portal vein TNF-a and plasma ALT increased continuously in the l/R group at I and 3 hours of reperfusion compared with the SH group; however, they declined significantly in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved in the I/R-NAC group compared with the I/R group (P<0.05). CONCLUSIONS: TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

N-acetylcysteine does not prevent post-endoscopic retrograde cholangiopancreatography hyperamylasemia and acute pancreatitis

AIM： Acute pancreatitis （AP） is the most common and often severe complication of endoscopic retrograde cholangiopancreatography （ERCP）. The early step in the pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals. N-acetylcysteine - a free radical scavenger may be potentially effective in preventing post-ERCP acute pancreatitis and it is also known that N-acetylcysteine （ACC） can reduce the severity of disease in experimental model of AP. METHODS： One hundred and six patients were randomly allocated to two groups. Fifty-five patients were given N-acetylcysteine （two 600 mg doses orally 24 and 12 h before ERCP and 600 mg was given iv, twice a day for two days after the ERCP）. The control group consisted of 51 patients who were given iv. isotonic saline twice a day for two days after the ERCP. Serum and urine amylase activities were measured before ERCP and 8 and 24 h after the procedure. The primary outcome parameter was post-ERCP acute pancreatitis and the secondary outcome parameters were differences between groups in serum and urine amylase activity. RESULTS： There were no significant differences in the rate of post-ERCP pancreatitis between two groups （10 patients overall, 4 in the ACC group and 6 in the controlgroup）. There were also no significant differences in baseline and post-ERCP serum and urine amylase activity between ACC group and control group. CONCLUSION： N-acetylcysteine fails to demonstrate any significant preventive effect on post-ERCP pancreatitis, as well as on serum and urine amylase activity.

N-acetylcysteine treats intravenous amiodarone induced liver injury

We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some commonality.Because IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases.

Neuroprotective effects of combined lead and cadmium,as well as N-acetylcysteine,on cerebral cortical neurons following lipid peroxidation injury

BACKGROUND： Studies have reported the antioxidant effects of lead and cadmium in the central nervous system, but very few have addressed the combined toxicity of lead and cadmium. The mechanisms by which these combined heavy metals are toxic, as well as how to protect cells from these agents, remains poorly understood. OBJECTIVE： Primary cultured rat cortical neurons were used to determine the effects of combined lead and cadmium on levels of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, catalase （CAT）, and acetylcholinesterase （ACHE）, as well as malondialdehyde （MDA）, and to evaluate the neuroprotective effects of N-acetylcysteine （NAC）. DESIGN, TIME AND SETTING An in vitro toxicological observation was performed at the Comparative Medicine Center of Yangzhou University from August 2007 to April 2008. MATERIALS： Lead acetate, cadmium acetate, and NAC were purchased from Sigma-Aldrich （St. Louis, USA）. Commercial kits of GSH-Px, SOD, CAT, ACHE, and MDA were purchased from Nanjing Jiancheng Bioengineering Institute, Nanjing, China. METHODS： The cerebral cortical neurons were isolated from newborn Sprague dawley rats at 24 hours after birth and primary cultured for 6 days. Thereafter, the cells were treated with a range of cadmium doses （0, 5.0, and 10.0μmol/L）, lead doses （0, 1.0, and 2.0 μmol/L）, or a combination of the two for 12 hours at 37℃in a 5% CO2 incubator, respectively. In addition, the cells were incubated with different doses of cadmium and/or lead and （0 and 50 μmol/L） NAC for 12 hours to assess the protective effects on cell survival. MAIN OUTCOME MEASURES： The activity of SOD, GSH-Px, CAT, and ACHE, as well as MDA content, in the cell lysates was detected using commercial kits. RESULTS： At 12 hours after treatment, compared to the control group, activity of GSH-Px, SOD, and AChE in the lead, cadmium, or combined treated cells was significantly decreased with increasing doses of cadmium/or lead （P 〈 0.05）, but CAT activity and MDA levels were significantly increased （P 〈 0.05）. The combination of cadmium and lead led to higher levels of toxicity than individual exposure. CONCLUSION： The degree of oxidative damage increased when the two heavy metals were combined. NAC protected neonatal cortical neurons by increasing activity of anti-oxidative enzymes and reducing lipid peroxidation, but the reduction was not statistically significant.

N-acetylcysteine and glycyrrhizin combination:Benefit outcome in a murine model of acetaminophen-induced liver failure

BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries.Substantial progress has been made in understanding the mechanism of hepatocellular injury,but N-acetylcysteine remains the only effective treatment despite its short therapeutic window.Thus,other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced hepatotoxicity.Our interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1(HMGB1)protein,a member of the family of damage-associated molecular pattern,known to play an important pathological role in various diseases.AIM To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver toxicity.METHODS Eight-week-old C57BL/6J wild-type female mice were used for all our experiments.Mice fasted for 15 h were treated with acetaminophen(500 mg/kg)or vehicle(phosphate-buffered saline)by intraperitoneal injection and separated into the following groups:Glycyrrhizin(200 mg/kg);N-acetylcysteine(150 mg/kg);and N-acetylcysteine/glycyrrhizin.In all groups,mice were sacrificed 12 h following acetaminophen administration.The assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase.Hepatotoxicity was also evaluated by histological examination of hematoxylin and eosin-stained tissues sections.Survival rates were compared between various groups using Kaplan-Meier curves.RESULTS Consistent with data published in the literature,we confirmed that intraperitoneal administration of acetaminophen(500 mg/kg)in mice induced severe liver injury as evidenced by increases in alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis score.Glycyrrhizin administration was shown to reduce the release of HMGB1 and significantly decreased the severity of liver injury.Thus,the co-administration of glycyrrhizin and N-acetylcysteine was investigated.Administered concomitantly with acetaminophen,the combination significantly reduced the severity of liver injury.Delayed administration of the combination of drugs,2 h or 6 h after acetaminophen,also induced a significant decrease in hepatocyte necrosis compared to mice treated with N-acetylcysteine alone.In addition,administration of N-acetylcysteine/glycyrrhizin combination was associated with an improved survival rate compared to mice treated with only N-acetylcysteine.CONCLUSION We demonstrate that,compared to N-acetylcysteine alone,co-administration of glycyrrhizin decreases the liver necrosis score and improves survival in a murine model of acetaminophen-induced liver injury.Our study opens a potential new therapeutic pathway in the prevention of acetaminophen hepatotoxicity.

Role of N-acetylcysteine in rifampicin-induced hepatic injury of young rats

AIM, To study the role of N-acetylcysteine （NAC） as a protective agent in rifampicin （RMP）-induced oxidative hepatic injury of young rats. METHODS： Hepatic injury was produced by giving 50mg/kg body weight/day of RMP for 3 wk. A dose of NAC （100mg/kg body weight/day） was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P4se, superoxide dismutase （SOD）, catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations. RESULTS： RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol （GSH） status was well preserved. Cytochrome P450 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels. CONCLUSION. NAC protects young rats against RMP- induced oxidative hepatic injury.

N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats

AIM: To evaluate the antioxidant effect of N-acetylcysteine(NAC) on the stomach of rats with portal hypertension.METHODS: Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups(n =6 each): Sham-operated(SO),SO + NAC,partial portal vein ligation(PPVL),and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg(i.p.) diluted in 0.6 m L of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution(0.6 m L) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15 th day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After,we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase(e NOS),vascular endothelial growth factor(VEGF),and nitrotirosine(NTT) proteins in stomach. We also evaluated e NOS and VEGF by Western blot analysis and assessed DNA damage in blood samples by the comet assay.RESULTS: The portal hypertension group exhibited increases in portal pressure when compared to SO group(29.8 ± 1.8 vs 12.0 ± 0.3 mm Hg)(P < 0.001). The same was observed when we compared the e NOS(56.8 ± 3.7 vs 13.46 ± 2.8 pixels)(P < 0.001),VEGF(34.9 ± 4.7 vs 17.46 ± 2.6 pixels)(P < 0.05),and NTT(39.01 ± 4.0 vs 12.77 ± 2.3 pixels)(P < 0.05) expression by immunohistochemistry of the PPVL animals with the SO group. The expression of e NOS(0.39 ± 0.03 vs 0.25 ± 0.03 a.μ)(P < 0.01) and VEGF(0.38 ± 0.04 vs 0.26 ± 0.04 a.μ)(P < 0.01) were also evaluated by Western blot analysis,and we observed an increase of both proteins on PPVL animals. We also evaluated the DNA damage by comet assay,and observed an increase on damage index and damage frequency on those animals. NAC decreased portal pressure values in PPVL + NAC animals(16.46 ± 2 vs 29.8 ± 1.8 mm Hg)(P < 0.001) when compared to PPVL. The expression of e NOS(14.60 ± 4.1 vs 56.8 ± 3.7 pixels)(P < 0.001),VEGF(19.53 ± 3.2 vs 34.9 ± 4.7 pixels)(P < 0.05) and NTT(21.84 ± 0.7 vs 39.01 ± 4.0 pixels)(P < 0.05) evaluated by immunohistochemistry were also reduced in PPVL + NAC animals. Also,when evaluated by Western blot e NOS expression(0.32 ± 0.03 vs 0.39 ± 0.03 a.μ)(P < 0.05) and VEGF expression(0.31 ± 0.09 vs 0.38 ± 0.04 a.μ)(P < 0.01). Furthermore,NAC modulated DNA damage in PPVL + NAC animals.CONCLUSION: In view of these results,we believe NAC is able to protect the stomach from the alterations induced by the PPVL procedure.

Anti-inflammatory and anti-apoptotic effects of N-acetylcysteine in diabetic rat corneal epithelium

AIM:To characterize the anti-inflammatory and antiapoptotic effects of N-acetylcysteine(NAC)in streptozotocin(STZ)-induced diabetic rat corneal epithelium and human corneal epithelial cells(HCECs)exposed to a high-glucose environment.METHODS:HCECs were incubated in 0,5,50 mmol/L glucose medium,or 50 mmol/L glucose medium with NAC for 24h.Diabetes was induced in rats by intraperitoneal injection of 65 mg/kg STZ and some of these rats were topically administered NAC to corneas with 3 mice per group.We characterized receptor for advanced glycation end-products(RAGE)expression using immunofluorescence,and interleukin(IL)-1βand cleaved caspase-3(CCAP-3)expression using immunohistochemistry.Circulating tumor necrosis factor(TNF)-αconcentration was measured by ELISA and cleaved poly-ADP ribose polymerase(PARP)concentration was quantified by Western blotting.Apoptotic cells were detected using TUNEL assay and annexin V and propidium iodide staining.RESULTS:Diabetic rats had higher expression of RAGE(2.46±0.13 fold),IL-1β,and CCAP-3 in apoptotic cells of their corneas than control rats.The expression of RAGE(1.83±0.11 fold),IL-1β,and CCAP-3,and the number of apoptotic cells,were reduced by topical NAC treatment.HCECs incubated in 50 mmol/L glucose medium showed high concentrations of TNF-α(310±2.00 pg/mL)and cleaved PARP(7.43±0.56 fold),and more extensive apoptosis than cells in 50 mmol/L glucose medium.However,the addition of NAC reduced the concentrations of TNF-α(153.67±2.31 pg/mL)and cleaved PARP(5.55±0.31 fold)and the number of apoptotic cells.CONCLUSION:NAC inhibits inflammation and apoptosis in the corneas of diabetic rats and HCECs maintained in a high-glucose environment.

N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis

AIM: To evaluate attenuating properties of N-acetylcysteine (NAC) on oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (NASH). METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 8) was free accessed to regular dry rat chow (RC) for 6 wk. Group 2 (NASH, n = 8) was fed with 100% fat diet for 6 wk. Group 3 (NASH + NAC20, n = 9) was fed with 100% fat diet plus 20 mg/kg per day of NAC orally for 6 wk. All rats were sacrificed to collect blood and liver samples at the end of the study. RESULTS: The levels of total glutathione (GSH) and hepatic malondialdehyde (MDA) were increased significantly in the NASH group as compared with the control group (GSH; 2066.7 ± 93.2 vs 1337.5 ± 31.5 μmol/L and MDA; 209.9± 43.9 vs 3.8 ±1.7 μmol/g protein, respectively, P < 0.05). Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. NAC treatment improved the level of GSH (1394.8 ± 81.2 μmol/L, P < 0.05), it did not affect MDA (150.1 ± 27.0 μmol/g protein), but led to a decrease in fat deposition and necroinflammation. CONCLUSION: NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.

Antimicrobial activity of alexidine alone and associated with N-acetylcysteine against Enterococcus faecalis biofilm

The purpose of this study was to assess the efficacy of alexidine（ALX）,alone and combined with N-acetylcysteine（NAC）,in eradicating two Enterococcus faecalis strain biofilms.The biofilms of E.faecalis ATCC 29212 and the clinical isolate E.faecalis D1 were grown in the MBEC-high-throughput device for 24 h and were exposed to five twofold dilutions of ALX（2%–0.007 8%）alone and combined with100 mg？mL21NAC,for 1 and 5 min.Eradication was defined as 100%kill of biofilm bacteria.The Student’s t-test was used to compare the efficacy of the associations of the two irrigants.After 1-min contact time,ALX eradicated the biofilms at all concentrations except for 0.007 8%and 0.015 6%–0.007 8%with E.faecalis ATCC 29212 and E.faecalis D1,respectively.Similar results for eradication and concentration were obtained when it was combined with 100 mg？mL21NAC.After 5 min of contact time,ALX alone and combined with NAC eradicated all enterococci biofilms.ALX showed antimicrobial properties against the two E.faecalis strain biofilms tested at very low concentrations,and its combined use with NAC was not seen to enhance its activity.

N-acetylcysteine in acute pancreatitis

Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various cell components causing lipid peroxidation, disturbances in calcium homeostasis and DNA damage, which lead to increased cell injury and eventually cell death. This review presents the most recent data concerning the effects of N-Acetylcysteine (NAC), in the treatment of AP. NAC is an antioxidant capable of restoring the levels of Glutathione, the most important cellular antioxidant. Studies show the benef icial effects of NAC treatment in preventing OFR production and therefore attenuating oxidative damage. Additionally, NAC treatment has been shown to prevent the increase in cytosolic Ca2+ concentration and reduce the accumulation of enzymes in acinar cells during AP. The prevention, by NAC, of these pathological events occurring within acinar would contribute to reducing the severity of AP. NAC is also capable of reducing the activation of transcription factors especially sensitive to the cellular redox state, such as Nuclear factor-κB, signal transducer and activator of transcription-3 and mitogenactivated protein kinase. This leads to a down-regulation of cytokines, adhesion molecules and chemokine expression in various cell types during AP. These f indingspoint to NAC as a powerful therapeutic treatment, attenuating oxidative-stress-induced cell injury and other pathological events at early stages of AP, and potentially contributing to reducion in the severity of disease.

N-acetylcysteine attenuates ischemia/reperfusion-induced cardiocyte apoptosis in diabetic rats

Objective：To study the effects of N-acetylcysteine （NAC） on ischemia/ reperfusion （I/R）-induced myocyte apoptosis in diabetic rats. Methods：The I/R heart model was made by ligation of the left anterior descending coronary artery （LAD） close to its origin. The LAD was occluded for 30 min followed by removal of ligation to allow subsequent reperfusion for 3 h. 72 rats were randomly divided into two groups , non-diabetic group （C, n = 36） and diabetic group ,（D, n = 36）. The animals in C group were randomly reassigned into sham-operated group （CS, n = 12） , I/R group （C I/R, n = 12） and treated with NAC group （CN, n = 12）. The rats in D group were also reassigned to sham-operated group （DS, n = 12） , I/R group （DI/R, n = 12） and treated with NAC group （DN, n = 12）. Malondialdehyde （MDA） and creatine kinase isoenzyme-MB （CK-MB） were measured. Infarct size（IS/AAR%）, the apoptosis index（AI） by TUNEL staining, the number of the cells positive for Caspase-3 and positive expression index （PEI） were calculated. Results：After I/R, the IS/AAR%, CK-MB, MDA, AI and Caspase-3 PEI were higher in diabetic group than those in non-diabetic group. Treatment with NAC decreased the above parameters in both non-diabetic and diabetic rats, but the parameters in diabetic rats were higher than those in non-diabetic rats. Conclusion：Diabetic rat hearts are more susceptible to I/R-induced myocardial necrosis and myocyte apoptosis. NAC can decrease the infarct size and attenuate cardiomyocyte apoptosis in both non-diabetic and diabetic rats, but the therapeutic effects are less effective in diabetic rats than those in non-diabetic rats.