PMID: 

Shock. 2019 Dec ;52(6):622-630. PMID: 30676497

Abstract Title: 

N-Acetylcysteine Ameliorates Gentamicin-Induced Nephrotoxicity by Enhancing Autophagy and Reducing Oxidative Damage in Miniature Pigs.

Abstract: 

The clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. Adult mini pigs were divided into isotonic saline solution, gentamicin, and gentamicin plus NAC combination treatment groups. Gentamicin-induced histopathological changes, including inflammatory cell infiltration and tubular necrosis, were attenuated by NAC. NAC ameliorated the gentamicin-induced decreases in the levels of autophagy-related proteins, such as LC3 (microtubule-associated protein 1 light chain 3), PINK1 (phosphatase and tensin homologue deleted on chromosome10-induced kinase 1), phospho-parkin, AMBRA1 (activatingmolecule in Beclin 1-regulated autophagy), p62/SQSTM1 (sequestosome protein 1), and polyubiquitinated protein aggregates. NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls,γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2'-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These resultssuggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.

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PMID: 

Reprod Biol Endocrinol. 2019 Feb 16 ;17(1):24. Epub 2019 Feb 16. PMID: 30771790

Abstract Title: 

Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men.

Abstract: 

BACKGROUND: Infertile men have higher levels of semen reactive oxygen species (ROS) than fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This study investigated the effects of supplementation with N-acetyl-cysteine (NAC) on the sperm quality, chromatin integrity and levels of oxidative stress in infertile men.METHODS: The study was carried out in the unit of ACECR Infertility Research Center, Qom, Iran. The patients consisted of 50 infertile men with asthenoteratozoospermia who received NAC (600 mg/d) orally for 3 months, after which they were compared with pre-treatment status. Semen was analyzed according to WHO (2010), followed by the assessment of protamine content [chromomycin A3 (CMA3)] and DNA integrity [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)]. Oxidative stress markers, i.e. total antioxidant capacity (TAC) and malondialdehyde (MDA), as well as hormonal profile (LH, FSH, Testosterone and Prolactin) were determined by ELISA kit.RESULTS: After NAC treatment, patients' sperm count and motility increased significantly whereas abnormal morphology, DNA fragmentation and protamine deficiency showed significant decreases compared to pre-treatment levels (P 

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PMID: 

Wounds. 2019 04 ;31(4):91-96. Epub 2019 Feb 14. PMID: 30802208

Abstract Title: 

Topical and Systemic Effects of N-acetyl Cysteine on Wound Healing in a Diabetic Rat Model.

Abstract: 

OBJECTIVE: This study evaluates the effects of topical and systemic N-acetyl cysteine (NAC) treatment on wound healing in a diabetic rat model.MATERIALS AND METHODS: A total of 48 male Wistar Albino rats were randomly divided into 4 groups of 12. Diabetes was induced with an intraperitoneal injection of 60 mg/kg streptozotocin. A 2-cm x 1-cm full-thickness wound was created on the back of each animal. In group 1 (control) and group 3 (systemic NAC), the wounds were closed with 0.9% sodium chloride-treated sterile gauze. In group 2 (topical NAC) and group 4 (topical + systemic NAC), the wounds were closed with sterile gauze treated with 3 mL (300 mg) of NAC. The animals in groups 3 and 4 were administered 200 mg/kg of NAC once daily through an orogastric tube. On days 1 and 14, the wounded areas were measured. Tissue and blood samples were taken on day 14 for histopathological and biochemical examination.RESULTS: On day 14, the wounded area in groups 2, 3, and 4 was found to be smaller than in group 1 (control). Histopathologically, epithelialization and fibrosis scores were significantly lower, whereas the inflammation score was higher in group 1 than in the other groups. Tissue oxidative stress parameters (malondialdehyde, fluorescent oxidation products, total oxidative stress) were higher in the control group than in the other groups. In groups 3 and 4 (which received systemic NAC), the oxidative stress parameters in serum samples were lower than those of the control group and group 2. Serum sulphydryl levels were the lowest in group 1.CONCLUSIONS: The results of this study show that both topical and systemic administration of NAC improved wound healing in a diabetic rat model. This effect of NAC may be related to its antioxidant properties since a reduction in oxidative stress parameters in both tissue and serum were shown in the present study.

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PMID: 

J Antimicrob Chemother. 2019 Aug 1 ;74(8):2188-2196. PMID: 31102529

Abstract Title: 

N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli.

Abstract: 

BACKGROUND: Fluoroquinolones such as ciprofloxacin induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS). Both the SOS response and ROS increase bacterial mutagenesis, fuelling the emergence of resistant mutants during antibiotic treatment. Recently, there has been growing interest in developing new drugs able to diminish the mutagenic effect of antibiotics by modulating ROS production and the SOS response.OBJECTIVES: To test whether physiological concentrations of N-acetylcysteine, a clinically safe antioxidant drug currently used in human therapy, is able to reduce ROS production, SOS induction and mutagenesis in ciprofloxacin-treated bacteria without affecting antibiotic activity.METHODS: The Escherichia coli strain IBDS1 and its isogenic mutant deprived of SOS mutagenesis (TLS-) were treated with different concentrations of ciprofloxacin, N-acetylcysteine or both drugs in combination. Relevant parameters such as MICs, growth rates, ROS production, SOS induction, filamentation and antibiotic-induced mutation rates were evaluated.RESULTS: Treatment with N-acetylcysteine reduced intracellular ROS levels (by∼40%), as well as SOS induction (by up to 75%) and bacterial filamentation caused by subinhibitory concentrations of ciprofloxacin, without affecting ciprofloxacin antibacterial activity. Remarkably, N-acetylcysteine completely abolished SOS-mediated mutagenesis.CONCLUSIONS: Collectively, our data strongly support the notion that ROS are a key factor in antibiotic-induced SOS mutagenesis and open the possibility of using N-acetylcysteine in combination with antibiotic therapy to hinder the development of antibiotic resistance.

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PMID: 

Clin Pharmacol Ther. 2019 Oct ;106(4):884-890. Epub 2019 Jul 17. PMID: 31206613

Abstract Title: 

N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease.

Abstract: 

This study assessed the biological and clinical effects in patients with Parkinson's disease (PD) of N-acetyl-cysteine (NAC), the prodrug to l-cysteine, a precursor to the natural biological antioxidant glutathione. Forty-two patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for 3 months or standard of care only. Participants received prebrain and postbrain imaging with ioflupane (DaTscan) to measure dopamine transporter (DAT) binding. In the NAC group, significantly increased DAT binding was found in the caudate and putamen (mean increase from 3.4% to 8.3%) compared with controls (P 

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PMID: 

J Food Biochem. 2019 Aug ;43(8):e12950. Epub 2019 Jun 18. PMID: 31368551

Abstract Title: 

Ameliorative effects of N-acetyl cysteine on diclofenac-induced renal injury in male rats based on serum biochemical parameters, oxidative biomarkers, and histopathological study.

Abstract: 

Diclofenac (DIC) can cause nephrotoxicity in humans. In this study, we evaluated the protective effects of N-acetyl cysteine (NAC) on DIC-induced nephrotoxicity. Rats were assigned to four groups. Group 1 was control group; group 2 administrated with DIC only; group 3 administrated with DIC plus NAC and group 4 was treated with DIC and silymarin. Then, the oxidative biomarkers in serum and kidney were evaluated. In group 2, DIC caused a remarkable elevation (p 

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PMID: 

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2019 Aug 30 ;41(4):529-535. PMID: 31484617

Abstract Title: 

[Effect of N-acetylcysteine on Cognitive Function and Nuclear Factor Erythroid 2 Related Factor 2/Heme Oxygenase-1 Pathway in Mouse Models of Postoperative Cognitive Dysfunction].

Abstract: 

To investigate the effect of N-acetylcysteine(NAC)on cognitive function and nuclear factor erythroid 2 related factor 2/ heme oxygenase-1(Nrf2/HO-1)pathway in mouse models of postoperative cognitive dysfunction. Methods Fifty-four male C57BL/6J mice(3-4 months old)were randomly divided into control group,surgery group,and surgery+NAC group by block randomization.The intramedullary fixation for left tibial fracture surgery was performed to establish postoperative cognitive dysfunction models.NAC(150 mg/kg)was administered intraperitoneally in group surgery+NAC 30 minutes before and 3 hours,6 hours after surgery,while saline was given in control group and surgery group.Six mice in each group were selected randomly underwent Morris water maze test on the third day after surgery.Animals were sacrificed at the first and third postoperative days,and the hippocampus was harvested.Enzyme-linked immunosorbent assay was used to quantify the levels of interleukin-6(IL-6)and malondialdehyde(MDA)in hippocampus.Western blot and real-time polymerase chain reaction were used to measure the expressions of Nrf2 and HO-1 in hippocampus. Results There was no significant difference in swimming speed among three groups(=2.135,=0.114).Compared with control group and surgery+NAC group,the surgery group had prolonged escape latency(

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PMID: 

Arch Physiol Biochem. 2019 Oct ;125(4):332-343. Epub 2018 Apr 17. PMID: 29663826

Abstract Title: 

Antioxidant and hepato-preventive effect ofextract against carbon tetrachloride-induced hepatotoxicity in rats and characterisation of its bioactive compounds by HPLC-MS.

Abstract: 

The objective of this study is to explore the preventive effects of ethyl acetate fraction fromleaf extract (EACA), associated with its phytochemical content, against the toxic impacts of acute exposure to carbon tetrachloride (CCl) in the liver of adult rats. HPLC analysis of ethyl acetate fraction from extractrevealed eight compounds. Administration of a single dose of CClcaused hepatoxicity as monitored by an increase in lipid peroxidation (thiobarbituric acid reactive substances) and in protein carbonyl level but a decrease in antioxidant markers in the liver tissue. The pre-treatment with EACA; significantly prevented the increased plasma levels of hepatic markers and lipid levels induced by CClin rats. Furthermore, this fraction ameliorated biochemical and histological parameters as compared to CCl-treated group. Our results suggest thatcontains promising substances to counteract the CClintoxication and can be efficient in the prevention of hepatotoxicity complications.

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PMID: 

Molecules. 2019 Nov 13 ;24(22). Epub 2019 Nov 13. PMID: 31766122

Abstract Title: 

The Anti-Aging Potential of Neohesperidin and Its Synergistic Effects with Other Citrus Flavonoids in Extending Chronological Lifespan ofBY4742.

Abstract: 

The anti-aging activity of many plant flavonoids, as well as their mechanisms of action, have been explored in the current literature. However, the studies on the synergistic effects between the different flavonoid compounds were quite limited in previous reports. In this study, by using a high throughput assay, we tested the synergistic effects between different citrus flavonoids throughout the yeast's chronological lifespan (CLS). We studied the effect of four flavonoid compounds including naringin, hesperedin, hesperitin, neohesperidin, as well as their different combinations on the CLS of the yeast strain BY4742. Their ROS scavenging ability, in vitro antioxidant activity and the influence on the extracellular pH were also tested. The results showed that neohesperidin extended the yeast's CLS in a concentration-dependent manner. Especially, we found that neohesperidin showed great potential in extending CLS of budding yeast individually or synergistically with hesperetin. The neohesperidin exhibited the strongest function in decreasing the reactive oxygen species (ROS) accumulation in yeast. These findings clearly indicated that neohesperidin is potentially an anti-aging citrus flavonoid, and its synergistic effect with other flavonoids on yeast's CLS will be an interesting subject for future research of the anti-aging function of citrus fruits.

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PMID: 

Pharmacol Res. 2019 10 ;148:104460. Epub 2019 Sep 24. PMID: 31560944

Abstract Title: 

Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota.

Abstract: 

Neohesperidin (NHP), derived from citrus fruits, has attracted considerable interest due to its preventative and therapeutic effects on numerous diseases. However, little progress has been made in determining the exact function of NHP on tumorigenesis. In the current study, we found that NHP inhibited colorectal tumorigenesis in the APCtransgenic mouse model, as well as induced apoptosis and blocked angiogenesis in vivo. Our in-cell study suggested that this tumorigenic preventative effect of NHP is not due to the direct impact on tumor cells. Intriguingly, by utilizing 16 s rRNA gene-based microbiota sequencing, the relative abundance of Bacteroidetes was decreased, while Firmicutes and Proteobacteria were increased in the presence of NHP. Additionally, the fecal microbiota transplantation experiment further revealed that feeding with fecal of NHP-treated mice induced considerable inhibition of tumorigenesis, which indicates that the alteration of gut microbiota is responsible for NHP-mediated prevention of colorectal tumorigenesis. Thus, our study not only suggests the efficacy of NHP as a potent natural product for preventing colorectal cancer but also proposes a compelling model to connect the gut microbiota to the preventative effect of NHP on tumorigenesis.

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