Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model

Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.

Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice

Acetaminophen (APAP) is commonly used as analgesic and antipyretic drug for relieving mild and moderate pain, but at high doses produces hepatic necrosis. Though, Obeticholic acid (OCA) has been tested in range of diseases, its therapeutic potential against APAP-induced hepatic injury remains to be elucidated. Thus, in this study, we investigated the preventive effect of OCA along with N-acetylcysteine (NAC) and Silymarin (SIL) against acetaminophen-induced hepatotoxicity in mice. SIL (100 mg/kg, po) and OCA (30 mg/kg, po) were administered continuously for six days prior to APAP administration. After sixth dose, animas were fasted for 12 h and treated with 300 mg/kg APAP and then received SIL (100 mg/kg, po), NAC (500 mg/kg, ip) and OCA (30 mg/kg, po) at 1 h after APAP. Mice were sacrificed 6 h after APAP injection. Analysis of serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), liver glutathione (GSH) and histopathology were employed for assessment of hepatotoxicity. APAP group showed a significant increase in ALT, AST, ALP and centriolobular hepatic necrosis with a significant decrease in glutathione in comparison to control group. All these parameters were significantly improved in all the three treated groups when compared to APAP group. In conclusion, Obeticholic acid (OCA), Silymarin (SIL) and N-acetylcysteine (NAC) are suggested to protect against APAP-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect and decreasing liver necrosis.

Follicular fluid from infertile women with mild endometriosis impairs in vitro bovine embryo development: potential role of oxidative stress / Fluido folicular de mulheres inférteis com endometriose leve prejudica o desenvolvimento in vitro de embriões bovinos: Potencial papel do estresse oxidativo

Abstract Objective To investigate whether follicular fluid (FF) from infertile women with mild endometriosis (ME) alters in vitro bovine embryo development, and whether the antioxidants N-acetyl-cysteine (NAC) and/or L-carnitine (LC) could prevent such damages. Methods Follicular fluid was obtained from infertile women (11 with ME and 11 control). Bovine oocytes were matured in vitro divided in: No-FF, with 1% of FF from control women (CFF) or ME women (MEFF); with 1.5mM NAC (CFF + NAC, MEFF + NAC), with 0.6mg/mL LC (CFF + LC, MEFF + LC), or both antioxidants (CFF + NAC + LC, MEFF + NAC + LC). After in vitro fertilization, in vitro embryo culture was performed for 9 days. Results A total of 883 presumptive zygotes were cultured in vitro. No differences were observed in cleavage rate (p = 0.5376) and blastocyst formation rate (p = 0.4249). However, the MEFF group (12.5%) had lower hatching rate than the No-FF (42.1%, p = 0.029) and CFF (42.9%, p = 0.036) groups. Addition of antioxidants in the group with CFF did not alter hatching rate (p ≥ 0.56), and in groups with MEFF, just NAC increased the hatching rate [(MEFF: 12.5% versus MEFF + NAC: 44.4% (p = 0.02); vs MEFF + LC: 18.8% (p = 0.79); versus MEFF + NAC + LC: 30.8% (p = 0.22)]. Conclusion Therefore, FF from infertile women with ME added to medium of in vitro maturation of bovine oocytes impairs hatching rate, and NAC prevented these damages, suggesting involvement of oxidative stress in worst of oocyte and embryo quality of women with ME.

Resumo Objetivo Investigar se o fluido folicular (FF) de mulheres inférteis com endometriose leve (ME, na sigla eminglês) altera o desenvolvimento in vitro de embriões bovinos, e se os antioxidantes N-acetil-cisteína (NAC) e/ou L-carnitina (LC) poderiam prevenir possíveis danos. Métodos O FF foi obtido de mulheres inférteis (11 com ME e 11 controles). Oócitos bovinos foram maturados in vitro divididos em: sem FF (No-FF), com 1% de FF de mulheres controle (CFF) ou mulheres comME (MEFF); com 1,5mMde NAC (CFF + NAC, MEFF + NAC), com 0,6mg/mL de LC (CFF + LC, MEFF + LC), ou ambos antioxidantes (CFF + NAC + LC, MEFF + NAC + LC). Depois da fertilização in vitro, o cultivo in vitro de embriões foi realizado por 9 dias. Resultados Um total de 883 zigotos presumidos foram cultivados in vitro. Nenhuma diferença foi observada na taxa de clivagem (p = 0,5376) e na taxa de formação de blastocistos (p = 0,4249). Entretanto, o grupo MEFF (12.5%) teve menor taxa de eclosão de blastocistos do que os grupos No-FF (42,1%, p = 0,029) e CFF (42,9%, p = 0,036). Adição de antioxidantes no grupo comCFF não alterou a taxa de eclosão (p ≥ 0.56), e nos grupos com MEFF, somente a NAC aumentou a taxa de eclosão [(MEFF: 12.5% versus MEFF + NAC: 44.4% (p = 0.02); versus MEFF + LC: 18.8% (p = 0.79); versus MEFF + NAC + LC: 30.8% (p = 0.22)]. Conclusão Portanto, o FF de mulheres inférteis com ME adicionado ao meio de maturação in vitro de oócitos bovinos prejudica a taxa de closão embrionária, e a NAC preveniu esses danos, sugerindo o envolvimento do estresse oxidativo na piora da qualidade oocitária e embrionária de mulheres com ME.

The beneficial role of N-acetylcysteine as an adjunctive drug in treatment of COVID-19 patients in a tertiary care hospital in India: an observational study

Background: N-acetyl cysteine, a mucolytic agent, demonstrates free radical scavenging and anti-inflammatory properties, and prevents endothelial dysfunction by inhibition of NF-KB and formation of no adducts. This has a potential role to tackle cytokine storms, endothelial dysfunction and prothrombotic state observed in COVID-19 manifestations like ARDS and Multi organ dysfunction.Methods: Institution based descriptive cross sectional study, 164 patients from laboratory confirmed RT PCR positive COVID-19 patients, in the study period from 27th May 2020 to 10th August 2020, were assessed, in medical college Kolkata, a dedicated COVID-19 care facility.Results: It was observed that moderate-severe patients who received N-acetyl cysteine along with standard therapy had average hospital stay duration of 12 days, higher rate of discharge, average duration of oxygen therapy of 8 days, less number of deaths and reduced transfer to critical care facilities.Conclusions: N-acetyl cysteine can be considered as an adjunctive therapy with standard protocol driven care, due to its beneficial anti-inflammatory and free radical scavenging properties.

Potential Role Of Annona Squamosa Linn Extract And N-Acetyl Cysteine In Management Of Rifampicin-Induced Hepatoxicity In Rats

Objective: Rifampicin (RIF) could be a recognized therapeutic and preventive agent against tuberculosis. Still, high rates of many side effects and symptoms related to hepatotoxicity have identified during treatment. So, the current study was aimed to evaluate the antioxidant and hepatoprotective activity of methanolic extract of Annona Squamosa Linn (MEAS) and N-Acetyl Cysteine (NAC) against RIF induced hepatic injury in male rats. Methods: The hepatoprotective effects of MEAS (500 mg/kg b.wt.) and NAC (100 mg/kg b.wt.) or co-treatment were assessed in a model of hepatotoxicity by RIF (300 mg/kg b. wt.) in male rats daily for 21 d. Moreover, bilirubin, total protein, albumin, ALT, AST, ALP, GGT, MDA, and GSH were estimated. In addition, the levels of IL-6, IL-10, 8(OH)dG, and Bcl2 were evaluated. Results: The oral administration of MEAS and NAC or their combination resulted in significant reductions in the levels of bilirubin, albumin, hepato-specific markers namely ALT, AST, ALP, GGT, and MDA as compared to the RIF group. Furthermore, MEAS and NAC or the combination of MEAS and NAC treatment significantly up-regulated the levels of total protein, glutathione reductase with concomitant decrease in inflammatory marker level IL-6 and apoptotic marker level 8(OH)dG as well as increment the level of anti-inflammatory marker IL-10 and anti-apoptotic marker Bcl2 as compared to the RIF group. Histological examination of the liver tissue indicated that co-treatment with MEAS and NAC completely abolished the inflammation and degeneration in hepatocytes and restore the liver tissue to its normal structure. Conclusion: The present findings demonstrated that a co-treatment of MEAS and NAC seems to be more productive and curative than alone MEAS or NAC treatment and strongly compensated the liver damage induced by RIF.

Clomiphene citrate plus N-acetyl cysteine versus letrozole for induction of ovulation in infertile patients with polycystic ovarian disease: a randomized clinical trial

Background: Polycystic ovarian disease (PCOD), a common endocrine disorder with multisystem affection, is the most common cause of anovulatory infertility. Our objective is to evaluate the effect of using clomiphene citrate (CC) plus N-acetyl cysteine (NAC) versus letrozole in ovulation induction in infertile patients with PCOD.Methods: Reproductive-aged infertile women either primary or secondary diagnosed as PCOD according to Rotterdam criteria, 2003 were considered for enrollment. Eligible women for were recruited and randomized (1:1) to receive either CC 100 mg plus NAC 600 mg (CC+NAC arm) or letrozole 5 mg (NCT03241472, clinicaltrials.gov). All medications were started from day 3 of the menstrual cycle for 5 days. The primary outcome was the ovulation rate in both groups. Secondary outcomes included the mid-cyclic endometrial thickness, ovarian hyperstimulation, and clinical pregnancy and miscarriage rates.Results: One hundred ten patients were enrolled and randomized to CC+NAC arm (n=55) or letrozole (n=55). The ovulation rate in patients in letrozole arm was significantly higher than CC+NAC arm (71.8% versus 53.2%, p=0.01). Additionally, endometrial thickness was higher in letrozole arm (mean±SD: 11.46±1.61 versus 9.0±1.13, p=0.031). However, no statistical significant difference with regarding the ovarian hyperstimulation rate (1.8% versus 3.6%, p=0.157), clinical pregnancy rate [3/19 patients (27.3%) versus 19/55 (34.5%), p=0.409] and miscarriage rate [4/15 patients (26.7%) versus 19/55 (15.8%), p=0.317] in CC+NAC versus letrozole groups respectively.Conclusions: Addition of NAC to CC in ovulation induction leads to comparable pregnancy rate as letrozole. However, letrozole produces high ovulation rate and the better mid-cyclic endometrial thickness.

N-Acetyl-cysteine protects A549 cells in paraquat-induced epithelial-mesenchymal transition / 中华急诊医学杂志

Objective To investigate the regulatory mechanism of Paraquat (PQ)-induced epithelial-mesenchymal transition (EMT) and the protective mechanism of N-acetyl-cysteine (NAC) in PQ-induced A549 cells by EMT markers (E-cadherin and α-smooth muscle actin).Methods EMT model was established by 30 μmol/L PQ-exposed A549 cells for 4 d.The application of 10 mmol/L NAC was incubated with A549 cells for 2 h in advance.Morphological changes of A549 cells were observed under light microscope.Western blot was used to detect the expression levels of TGF-β1,E-cadherin and α-smooth muscle actin.Results In PQ-induced EMT model,the PQ group showed typical morphological changes,and the cells changed from cobblestone-like epithelial appearance to spindle-shaped mesenchymal-like appearance compared to the control group.Westem blotting showed that the protein levels of TGF-β1 and α-smooth muscle actin in the PQ group were significantly increased and the protein levels of E-cadherin were decreased in the PQ group (all P＜0.05).NAC preincubation can effectively reverse the above changes caused by PQ exposure:the protein levels of E-cadherin and α-smooth muscle actin were significantly increased and decreased,respectively and morphological changes showed more cobblestonelike epithelial appearance.Conclusion Cell experiments showed that PQ exposure can cause EMT in epithelial cells,and NAC has a protective effect in this process.Thus,it may provide new ideas and strategies for the treatment of pulmonary fibrosis caused by PQ poisoning in clinical practice.

Multicenter Evaluation on the Efficacy of N-Acetyl Cystine in Relieving the Symptoms of Laryngopharyngeal Reflux Disease

BACKGROUND AND OBJECTIVES: Laryngopharyngeal reflux disease (LPRD) is relatively common disease. N-acetyl cysteine (NAC) has both mucolytic and antioxidant effect, also may be beneficial in inflammatory airway diseases. The purpose of this study was to evaluate the efficacy and safety of inhaled NAC therapy in LPRD. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 525 LPRD patients at 12 medical centers. Finally 401 patients subjected to inhaled NAC therapy for 2 months were enrolled in the study. We analyzed the change of Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) after use of NAC for 4 weeks and 8 weeks in addition to the patient's compliance of the treatment. RESULTS: The RSI score significantly decreased from 19.87±6.34 to 12.78±6.93 after 4 weeks and to 10.65±7.47 after 8 weeks. The RFS score also significantly decreased from 9.29±3.4 to 7.17±3.41 after 4 weeks and to 6.1±3.73 after 8 weeks (p<0.05). During the treatment periods, 42 patients (10.4%) reported to have 80 episodes of discomfort. Throat discomfort (33%) and nausea (28%) were most common complaints, but the duration of discomfort was usually less than 4 weeks. CONCLUSION: Inhaled NAC treatment is highly effective for the reduction of both subjective and objective findings in LPRD patients. This study will provide the evidence of new treatment option for patients with LPRD. However, further studies will be needs to assess the real effect of inhaled NAC therapy as a standard treatment regimen of LPRD.

Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models

This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine. Circulating miR-146a and miR-206 were increased in cisplatin-induced nephrotoxicity and bupivacaine-induced myotoxicity, respectively. Taken together, these results indicate that circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury.

Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models

This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine. Circulating miR-146a and miR-206 were increased in cisplatin-induced nephrotoxicity and bupivacaine-induced myotoxicity, respectively. Taken together, these results indicate that circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury.

Efficacy and tolerability of fixed dose combination of silymarin, alpha lipoic acid, N-acetyl cysteine and selenium in the management of some liver disorders

Globally liver disorders are major cause of illness death and death. Oxidative stress plays a critical role in the progression of alcoholic and nonalcoholic related diseases. The aim of the present study was to evaluate the efficacy and tolerability of fixed dose combination (FDC) of silymarin, alpha lipoic acid, N-acetyl cysteine and selenium in the management of liver disorders. This was an observational, non-randomized, open label, non-comparative, multi-centric post-marketing surveillance study. The above mentioned FDC was administered to 15 patients diagnosed with alcoholic or viral hepatitis for three months. Evaluation of liver function tests (LFT) were carried out at baseline and at the end of 3rd month of the treatment. Significant changes were observed in the LFT parameters at the end of three months of this study. aspartate aminotransferase (AST): (Mean ± SEM) 369.9 ± 128.0 to 97.00 ± 34.27 U/L, (p < 0.0001); alanine aminotransferase (ALT): 652.93 ± 214.57 to 194.40 ± 82.51 U/L, (p < 0.03); Alkaline phosphatase: 197.47 ± 25.57 to 151.60 ± 17.92 U/L, (p < 0.0059); Gamma glutamyl transferase: 156.67 ± 49.80 to 87.33 ± 22.94 U/L, (p < 0.0490); Total bilirubin: 3.44 ± 0.76 to 1.66 ± 0.57 mg/dL, (p < 0.0192) and bilirubin direct: 2.13 ± 0.58 to 1.00 ± 0.50 mg/dL, (p < 0.0273). Two patients reported mild gastrointestinal adverse events (nausea, bloating). This FDC was therapeutically effective under the circumstances of elevated oxidative stress and produces significant reduction in LFT parameters in alcoholic and viral hepatitis patients.

Pharmacotherapy in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis or cryptogenic fibrosing alveolitis is a form of chronic, progressive interstitial lung disease causing scarring of lung tissue and usually affect adults. Treatment is usually aimed at controlling inflammation and thus slowing the process of fibrosis. With only few patients responding to treatment and the disease being ultimately fatal with poor progression, the underlying lesion was considered to be fibrotic rather than inflammatory. Fibrotic foci, deposition of collagen, and lack of inflammatory cells are a predominant finding. Pirfenidone and N-acetyl cysteine are the only effective pharmacotherapy available till date. Interim results of PANTHER Trial clearly indicate more risk with triple therapy. However, in Indian patients, trial of steroid therapy may be tried when there is doubt of chronic hypersensitivity pneumonitis. BIBF 1120 has also shown positive results in Phase II clinical trial and shows a positive response in deteriorating lung function. Supplemental oxygen, education of patient, pulmonary rehabilitation, and Streptococcus pneumoniae and influenza vaccine are the most important supportive care. Pulmonary rehabilitation should be used as a treatment in the majority of patients.

Study of mechanism of DXM and NAC inhibiting expression of IL-8 and ICAM-1 in A549 cells / 中国药理学通报

Aim To study the mechanism of DXM and NAC inhibiting the expression of IL-8 and ICAM-1 in A549 cells. Methods The expression of IL-8 and ICAM-1 was detected by ELISA and flow cytometry re-spectively; the expression of GR,HDAC,AP-1,NF-κB was detected by Western blot, while the activity of HDAC was detected by spectrophotometry. ResultsThe increasing expression of IL-8 and ICAM-1 induced by TNF-α could be inhibited by DXM and NAC in A549 cells. DXM could inhibit the transcribed activa-tion of AP-1,NF-κB, and the expression of HDAC and its activity induced by TNF-α and LPS; NAC only in-hibited the transcribed activation of NF-κB, while it had no affection on the transcribed activation of AP-1 and the expression of HDAC and its activity. Conclu-sions DXM and NAC both have the anti-inflammatory effect. DXM plays the role of anti-inflammation through increasing the expression and activation of HDAC, in-hibiting the transcribed activation of AP-1 and NF-κB, while NAC has no effect on the expression and activa-tion of HDAC, which shows that NAC does not exert anti-inflammatory effect through acetylation signal.

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-á3 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.

Effect of N-Acetyl Cysteine administration to the degree of parasitemia and plasma interleukin-12 level of mice infected with plasmodium berghei and treated with artemisinin.

Introduction Protection against malaria requires a cell-mediated immune response which is initiated by releasing interleukin-12 (IL-12) from antigen presenting cells (APC). N-Acetyl Cysteine (NAC) is a precursor of glutathione, while glutathione itself increases IL-12 production. Treatment with NAC combined with artemisinin is supposed to increase cellular immunity of mice during Plasmodium berghei infection. The aim of this study was to measure the effects of NAC administration on the degree of parasitemia and plasma IL-12 level in mice infected with P. berghei and treated with artemisinin. Method The research was done using post-test-control-only design using 5 groups: group A (negative control group), group B (positive control group, or mice infected with P.berghei without therapy), group C ( mice infected by P.berghei and received artemisinin 0.04 mg/g BW for 7 days), group D (mice infected with P.berghei and received artemisinin in combination with NAC 1 mg/g BW for 7 days) and group E (mice infected wirth P.berghei and received artemisinin in combination with NAC 1 mg/g BW for 3 days and tapered into ½ mg/g BW for 4 days). Parasitemia was followed up every two days. Approximately six days post infection or when the degree of parasitemia reached ± 10% therapy was begun. On the 3rd, 5th, and 7th days post therapy, mice from each group were terminated and assayed for plasma IL-12 level (ELISA, Bender Medsystems GmbH, Vienna, cat. BMS6004). Results All mice treated with artemisinin mono-therapy and combined therapy had significantly decreased parasitemia (P=0.000). There was no significant difference (P>0.05) in decreasing parasitemia among treatment groups. The plasma IL-12 level increased significantly in both groups that received the combination of artemisinin and NAC constant dose and tapering dose compared with the group that received artemisinin mono-therapy (p < 0,05). Plasma IL-12p70 level in the combination of artemisinin and NAC tapering dose therapy group was higher than other groups on the 5th and 7th days post therapy. Conclusion The conclusion of this research is that artemisinin mono-therapy decreased parasitemia effectively as well as the combination therapy of artemisinin and NAC. Artemisinin and NAC therapy, constant and tapering dose, increase plasma IL-12p70 level more than artemisinin mono-therapy does. The highest plasma IL-12p70 level was found in the artemisinin plus NAC tapering dose therapy group with seven days duration of therapy.

Characterization of Gentamicin-Induced Apoptosis in a Cochlear Cell Model / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Aminoglycoside antibiotics are ototoxic. Understanding of the molecular mechanisms underlying the drug-induced ototoxicity, however, has been hampered by limited cell availability. Recently, HEI-OC1 cells, which are of an immortalized cochlear cell line sensitive to ototoxic drugs, have been derived from the auditory sensory organ. This study was performed to confirm whether cultured HEI-OC1 cells can be used to evaluate aminoglycoside-induced ototoxicity and the effect of antioxidants against aminoglycoside-induced colchlear cell damage. MATERIALS AND METHOD: Gentamicin was administered for 3 days in the media containing HEI-OC1 cells. RESULTS: Cell viability was decreased by gentamicin in a dose-dependent manner. The cell number was decreased by 50% 3 days after the exposure to 2 mM gentamicin. Penicillin did not have any significant effect. Flow cytometric analysis revealed that sub G1 arrest representing cellular apoptosis was accelerated by gentamicin treatment but not by penicillin. Expression of p27Kip1, the cyclin-dependent kinase inhibitor, was exclusively increased by gentamicin. Reactive oxygen species were also increased by gentamicin when compared with those of the control or when penicillin was used. Caspase-3 activity became increased according to the elevation of gentamicin concentrations. N-acetyl cysteine, but not vitamin E or vitamin C, ameliorated cell survival dose-dependently against gentamicin. CONCLUSION:The present study reveals that the HEI-OC1 cell line is a good model to evaluate gentamicin-induced ototoxicity. The results suggest that gentamicin-induced apoptosis may be, at least partially, linked to the overproduction of a reactive oxygen species called. Nacetyl cysteine, a free radical scavenger, that decreases the gentamicin ototoxicity.

Learning and Memory Damage Induced by Formaldehyde and Protective Effect of N-acetyi-cysteine in Mice / 环境与健康杂志

Objective To explore the adverse effects of formaldehyde(FA)on learning and memory ability of mice and the antagonistic effect of N-acetyl-cysteine(NAC),an antioxidant.Methods Thirty-four ICR mice were randomly divided into four groups,the control(NS,n=8),treated with FA(15 mg/kg,n=9),treated with NAC(100 mg/kg,n=8),treated with FA(15 mg/kg) plus NAC(100 mg/kg,n=9),the treatment was conducted by intraperitoneal injection once a day for seven consecutive days.On the eighth day,the learning and memory ability were tested by using water labyrinth task for seven consecutive days.Results The mice in FA group behaved excited,restless and then turned to repose,moveless and clustering,but this phenomena was not seen in the other groups.There was no significant difference in the body weight of mice among groups.As for learning,latent period in the FA group [(27.15?2.66)s] was significantly longer than that in the control group [(15.83?2.82)s] and the FA+ NAC group[(14.98?2.66)s],and revealed statistical significance(P

Effect of N-acetyl-cysteine on Allodynia in a Chronic Post-ischemia Pain Model of Rat

BACKGROUND: Complex regional pain syndrome type I (CRPS-I) is a clinical syndrome that is poorly understood and difficult to treat. Reactive oxygen species (ROS) and inflammatory responses may contribute to the development of CRPS-I. This study evaluated the effect of N-acetyl-cysteine (NAC) on both mechanical and cold allodynia in a rat CRPS-I model. METHODS: Male adult SD rats were used for the CRPS-I model that was produced following prolonged hindpaw ischemia/reperfusion. The rats were divided into 3 groups, Group O (-) (n = 8): rats without a tourniquet; Group O (+) (n = 8): rats received ischemic injury with a tourniquet on the hindpaw and they were reperfused 3 hours after the tourniquet application; and Group ON (+) (n = 8): rats received ischemic injury with a tourniquet ring on the hindpaw and they were reperfused 3 hours after the tourniquet application and they received intraperitoneal N-cetyl-ysteine (500 mg/kg) injection just after the tourniquet application and at 1 day and 2 days after the reperfusion. RESULTS: In the Group O (+), mechanical (von Frey hair) and cold (acetone exposure) allodynia were evident in the affected hindpaw as early as 1 day after reperfusion; this was extended for 2 weeks and it spread to the uninjured contralateral hindpaw. In the Group ON (+), the mechanical and cold allodynia were attenuated compared to those rats of Group O (+). CONCLUSIONS: NAC, a free radical scavenger, was able to reduce mechanical and cold allodynia in this model, and the generation of ROS is partly responsible for CRPS-I.

Change of Post-anesthetic Recovery Time after Colorectal Surgery with N-acetyl-cysteine Infusion / 대한마취과학회지

BACKGROUND: The gut is an important area for inflammatory responses. Gut manipulation during open laparotomy compared with laparoscopic surgery, increases the inflammatory responses. Laparoscopic assisted colectomy (LC) with less bowel manipulation might minimize the inflammatory responses and oxidative stress, and offer a faster postanesthetic recovery than an open colectomy (OC). This study evaluated the effect of N-acetyl-cysteine (NAC), an antioxidant, on the recovery after colectomy. METHODS: 116 colorectal tumor patients were reviewed retrospectively. The patients were divided into 3 groups; LC by surgeon A (A - L), OC by surgeon A (A - O) and OC by surgeon B (B - O). The postanesthetic recovery scores (PARS) were compared. In the prospective randomized controlled trial, the colorectal tumor patients were assigned to one of four groups; laparoscopic assisted colectomy (L - N) with NAC infusion (L + N), open colectomy (O - N) with NAC infusion (O + N). In the NAC groups, NAC (5 mg/kg/h) was infused after intubation to extubation. The PARS were compared. RESULTS: In the retrospective study, the time to reach 10 points, which satisfies the discharge criteria in the PACU, was significantly lower in the A-L group than in the other groups. In the prospective study, the time to 10 points was shorter in the O + N group than in the O-N group. NAC offered no added benefits to the L + N and L-N groups. CONCLUSIONS: NAC offered faster recovery in the OC group but not in the LC group.