N-acetyl cysteine prevents polymethyl methacrylate bone cement extract-induced cell death and functional suppression of rat primary osteoblasts

Background: The problem of bacterial colonization of implants used in medical practice continues to be relevant regardless of the material of the implant. Particular attention deserves polymeric implants, which are prepared ex tempore from polymethyl methacrylate, for example - duting orthopedic surgical interventions (so-called "bone cement"). The protection of such implants by antibiotic impregnation is subjected to multiple criticisms, therefore, as an alternative to antibiotics, lytic bacteriophages with a number of unique advantages can be used - however, no experimental studies have been published on the possibility of impregnating bacteriophages into polymethyl methacrylate and their antibacterial activity assessment under such conditions.Aims: to evaluate the possibility of physical placement of bacteriophages in polymethylmethacrylate and to characterize the lytic antibacterial effect of two different strains of bacteriophages when impregnated into polymer carrier ex tempore during the polymerization process in in vitro model.Materials and methods: First stage - Atomic force microscopy (AFM) of polymethyl methacrylate samples for medical purposes was used to determine the presence and size of caverns in polymethyl methacrylate after completion of its polymerization at various reaction temperatures (+6…+25°C and +18…+50°C).The second stage was performed in vitro and included an impregnation of two different bacteriophage strains (phage ph20 active against S. aureus and ph57 active against Ps. aeruginosa) into polymethyl methacrylate during the polymerization process, followed by determination of their antibacterial activity.Results: ACM showed the possibility of bacteriophages placement in the cavities of polymethyl methacrylate - the median of the section and the depth of cavities on the outer surface of the polymer sample polymerized at +18…+50°C were 100.0 and 40.0 nm, respectively, and on the surface of the transverse cleavage of the sample - 120.0 and 100.0 nm, respectively, which statistically did not differ from the geometric dimensions of the caverns of the sample polymerized at a temperature of +6…+25°C.The study of antibacterial activity showed that the ph20 bacteriophage impregnated in polymethyl methacrylate at +6…+25°C lost its effective titer within the first six days after the start of the experiment, while the phage ph57 retained an effective titer for at least 13 days.Conclusion: the study confirmed the possibility of bacteriophages impregnation into medical grade polymethyl methacrylate, maintaining the effective titer of the bacteriophage during phage emission into the external environment, which opens the way for the possible application of this method of bacteriophage delivery in clinical practice. It is also assumed that certain bacteriophages are susceptible to aggressive influences from the chemical components of "bone cement" and / or polymerization reaction products, which requires strict selection of bacteriophage strains that could be suitable for this method of delivery.

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N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

Journal of Diabetes Research ◽

10.1155/2020/9589507 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16 ◽

Cited By ~ 2

Author(s):

Xin Li ◽

Jane Kim ◽

Jiabin Wu ◽

Alaa’ I Ahamed ◽

Yinsheng Wang ◽

...

Keyword(s):

Cell Death ◽

Bacterial Cell ◽

Chronic Wounds ◽

Chronic Wound ◽

Diabetic Mouse ◽

Bacterial Survival ◽

Bacterial Cell Death ◽

Carboxylic Groups ◽

Acetyl Cysteine

Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with α-tocopherol, N-acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS). We hypothesize that NAC creates a microenvironment that affects bacterial survival and EPS integrity. To test this hypothesis, we developed an in vitro biofilm system using microbiome taken directly from diabetic mouse chronic wounds. For these studies, we chose mice in which chronic wound microbiome was rich in Pseudomonas aeruginosa (97%). We show that NAC at concentrations with pH < pKa causes bacterial cell death and breakdown of EPS. When used before biofilm is formed, NAC leads to bacterial cell death whereas treatment after the biofilm is established NAC causes biofilm dismantling accompanied by bacterial cell death. Mechanistically, we show that NAC can penetrate the bacterial membrane, increase oxidative stress, and halt protein synthesis. We also show that low pH is important for the actions of NAC and that bacterial death occurs independently of the presence of biofilm. In addition, we show that both the acetyl and carboxylic groups play key roles in NAC functions. The results presented here provide insight into the mechanisms by which NAC dismantles biofilm and how it could be used to treat chronic wounds after debridement (NAC applied at the start of culture) or without debridement (NAC applied when biofilm is already formed). This approach can be taken to develop biofilm from microbiome taken directly from human chronic wounds to test molecules that could be effective for the treatment of specific biofilm compositions.

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Efficacy of Adoptive T-cell Therapy Is Improved by Treatment with the Antioxidant N-Acetyl Cysteine, Which Limits Activation-Induced T-cell Death

Cancer Research ◽

10.1158/0008-5472.can-16-0587 ◽

2016 ◽

Vol 76 (20) ◽

pp. 6006-6016 ◽

Cited By ~ 20

Author(s):

Matthew J. Scheffel ◽

Gina Scurti ◽

Patricia Simms ◽

Elizabeth Garrett-Mayer ◽

Shikhar Mehrotra ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Cell Therapy ◽

Adoptive T Cell Therapy ◽

T Cell Therapy ◽

Acetyl Cysteine

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Enhancement of gallic acid-induced human pulmonary fibroblast cell death by N-acetyl cysteine and L-buthionine sulfoximine

Human & Experimental Toxicology ◽

10.1177/0960327110384528 ◽

2010 ◽

Vol 30 (8) ◽

pp. 992-999 ◽

Cited By ~ 3

Author(s):

Bo Ra You ◽

Woo Hyun Park

Keyword(s):

Cell Death ◽

Growth Inhibition ◽

Gallic Acid ◽

Buthionine Sulfoximine ◽

Fibroblast Cell ◽

Biological Properties ◽

Dependent Manner ◽

Toxicological Effect ◽

Acetyl Cysteine ◽

Pulmonary Fibroblast

Gallic acid (GA) has various biological properties including anti-cancer effect. However, little is known about the toxicological effect of GA in primary normal cells. Here, we evaluated the effects of GA on human pulmonary fibroblast (HPF) cells in relation to reactive oxygen species (ROS) and glutathione (GSH). GA inhibited the growth of HPF cells at 24 hours in a dose-dependent manner. GA also induced HPF cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). GA increased ROS levels including O2•- and GSH-depleted cell numbers in HPF cells at 24 hours. Treatment with 2 mM N-acetyl-cysteine (NAC) intensified growth inhibition and death in GA-treated HPF cells. NAC decreased ROS levels and increased GSH depletion in these cells. Treatment with 10 μM L-buthionine sulfoximine (BSO) also enhanced growth inhibition and death in GA-treated HPF cells. BSO increased ROS levels and GSH depletion in these cells. In conclusion, GA-induced HPF cell death was accompanied by ROS increase and GSH depletion. The changes of ROS and GSH levels by NAC and BSO appeared to affect cell growth and death in GA-treated HPF cells.

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N-Acetyl Cysteine as a Novel Polymethyl Methacrylate Resin Component: Protection against Cell Apoptosis and Genotoxicity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1301736 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Yu Zhang ◽

Jian-feng Xiao ◽

He-feng Yang ◽

Yang Jiao ◽

Wei-wei Cao ◽

...

Keyword(s):

Dna Damage ◽

Polymethyl Methacrylate ◽

Cell Apoptosis ◽

Oxidative Dna Damage ◽

Redox Regulation ◽

Protective Effects ◽

Mitochondrial Apoptosis ◽

Acetyl Cysteine ◽

Pmma Resin

The present study investigated the antiapoptotic and antigenotoxic capabilities of N-acetyl cysteine- (NAC-) containing polymethyl methacrylate (PMMA) resin. An in vitro Transwell insert model was used to mimic the clinical provisional restorations placed on vital teeth. Various parameters associated with cell apoptosis and genotoxicity were investigated to obtain a deeper insight into the underlying mechanisms. The exposure of human dental pulp cell (hDPC) cultures to the PMMA resin (Unifast Trad™) resulted in a rapid increase in reactive oxygen species (ROS) level beginning at 1 h, which was followed by time-dependent cell detachment and overt death. The formation of γ-H2AX and cell cycle G1 phase arrest indicated that oxidative DNA damage occurred as a result of the interactions between DNA bases and ROS, beyond the capacities of cellular redox regulation. Such oxidative DNA damage triggers the activation of p53 via the ataxia telangiectasia mutated (ATM) signaling pathway and the induction of intrinsic mitochondrial apoptosis. Oxidative stress, cell apoptosis, and DNA damage induced by the PMMA resin were recovered to almost the level of untreated controls by the incorporation of NAC. The results indicate that the PMMA resin induced the intrinsic mitochondrial apoptosis as a consequence of p53 activation via the ATM pathway in response to oxidative DNA damage. More importantly, the incorporation of NAC as a novel component into the Unifast Trad™ PMMA resin offers protective effects against cell apoptosis and genotoxicity. This procedure represents a beneficial strategy for developing more biocompatible PMMA-based resin materials.

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Polymethyl methacrylate does not adversely affect the osteogenic potential of human adipose stem cells or primary osteoblasts

Journal of Biomedical Materials Research Part B Applied Biomaterials ◽

10.1002/jbm.b.34501 ◽

2020 ◽

Vol 108 (4) ◽

pp. 1536-1545

Author(s):

Angela P. Bastidas‐Coral ◽

Astrid D. Bakker ◽

Cornelis J. Kleverlaan ◽

Jolanda M. A. Hogervorst ◽

Jenneke Klein‐Nulend ◽

...

Keyword(s):

Stem Cells ◽

Polymethyl Methacrylate ◽

Adipose Stem Cells ◽

Osteogenic Potential ◽

Primary Osteoblasts ◽

Human Adipose Stem Cells

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Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells

Toxicology and Industrial Health ◽

10.1177/0748233710365695 ◽

2010 ◽

Vol 26 (5) ◽

pp. 297-308 ◽

Cited By ~ 13

Author(s):

RM Satpute ◽

J. Hariharakrishnan ◽

R. Bhattacharya

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Caspase 3 ◽

Critical Role ◽

Total Antioxidant Status ◽

Protective Effects ◽

Simultaneous Treatment ◽

Acetyl Cysteine

Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625—1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.

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A comparative study on initial prothesis stability fixed by strontium-containing hydroxyapatite comparing with polymethyl methacrylate bone cement

10.5353/th_b4419326 ◽

2009 ◽

Author(s):

Ting Wang

Keyword(s):

Comparative Study ◽

Bone Cement ◽

Polymethyl Methacrylate

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Local antibiotic treatment of soft tissue and bone infections of the foot

Journal of the American Podiatric Medical Association ◽

10.7547/87507315-80-7-345 ◽

1990 ◽

Vol 80 (7) ◽

pp. 345-353 ◽

Cited By ~ 12

Author(s):

DE Stabile ◽

AM Jacobs

Keyword(s):

Soft Tissue ◽

Bone Cement ◽

Success Rate ◽

Polymethyl Methacrylate ◽

Antibiotic Treatment ◽

Soft Tissue Infection ◽

Definitive Diagnosis ◽

Histologic Examination ◽

Bone Infections ◽

Local Antibiotic

Twenty-seven pedal soft tissue and bone infections in 26 patients were treated with surgical necrectomy of infected tissues and implantation of antibiotic-loaded polymethyl methacrylate bone cement beads on chains. The definitive diagnosis of the infected tissues was obtained by culture and histologic examination in all of the cases. A wide variety of foot infections was successfully treated in this manner. The success rate without recurrence of osteomyelitis or soft tissue infection was 95% in this study at an average of 16 months after surgery.

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