Effect of N-acetylcysteine on Radiation-induced Genotoxicity and Cytotoxicity in Rat Bone Marrow

Demirel, Can; Kılçıksız, Sevil; Ay, Özlem İzci; Gürgül, Serkan; Ay, Mustafa; Erdal, Nurten

doi:10.1269/jrr.08066

Cited by 36 publications

(28 citation statements)

References 43 publications

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“…NAC is an excellent cytoprotective compound for hematopoietic cells, since it preserves parameters of blood formula and hemoglobin level, inhibits apoptosis upon carmustine treatment in rats, (El-Sayed et al, 2010) and decreases oxidative stress upon exposure to pesticides in peripheral blood mononuclear cells in humans (Ahmed et al, 2009). NAC exhibits good radioprotective qualities and improves clonogenic functions and long-term engraftment of HSC and HPC, and decreases genotoxicity and cytotoxicity effects in bone marrow upon irradiation in different mammal species (Demirel et al, 2009). ROS associated defects in FoxO and Atm deficient mice (models with increased ROS level in HSC) (Ito et al, 2004;Tothova et al, 2007) can also be rescued by NAC.…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine protects induced pluripotent stem cells from in vitro stress: impact on differentiation outcome

Berniakovich¹,

Laricchia-Robbio²,

Belmonte

2012

Int. J. Dev. Biol.

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Induced pluripotent stem cells (iPSCs) have the ability to differentiate towards various cell types of the adult organism and are a potential source of transplantable material in regenerative medicine. The entire process of conversion of iPSCs into terminally differentiated cells takes place in vitro and requires long periods of time. During in vitro culture, cells are exposed to environmental factors, which are capable of decreasing cellular performance and viability. Oxidative stress is the major underlying mechanism of such negative impact of in vitro environmental factors. We aimed to study the alteration of cellular properties during in vitro hematopoietic differentiation of human iPSCs and the ability of N-acetylcysteine (NAC), a potent free radical scavenger, to prevent such alterations. IPSCs were differentiated towards hematopoietic cells in the presence of 1 mM NAC. Intracellular reactive oxygen species (ROS), nitric oxide (NO), senescence, apoptosis and mitochondrial membrane potential (MMP) were evaluated at 1 and 3 weeks of differentiation. In the course of hematopoietic differentiation of iPSCs, cells progressively accumulated intracellular ROS and NO, increased the levels of apoptosis and senescence, and showed a decrease in mitochondrial functionality. NAC supplementation reversed all these phenomena. NAC administration also improved hematopoietic differentiation of iPSCs in terms of production of CD34, CD45 and CD43 positive cells. In conclusion, when supplemented during hematopoietic differentiation of iPSCs, NAC decreased oxidative stress, rescued the decline in cellular properties induced by long-term in vitro culture and promoted hematopoietic differentiation of iPSCs.

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Section: Introductionmentioning

confidence: 99%

N-acetylcysteine protects induced pluripotent stem cells from in vitro stress: impact on differentiation outcome

Berniakovich¹,

Laricchia-Robbio²,

Belmonte

2012

Int. J. Dev. Biol.

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“…The thiol group is reactive toward xenobiotics and seems to be responsible for the beneficial effects of cysteine in poisoning cases. 11,30 Both NAC and cysteine are known radioprotective agents whose radioprotective properties are attributable to the antioxidant and free radical scavenging characteristics of the thiol group. 10,11 The pKa values-the values at which half of the functional group are ionised-of the thiol group have been shown to play an important role in the radioprotective properties of these agents, in that the more the thiol is ionised, the greater the radioprotection.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 Serine is an analogue of cysteine, a well-known radioprotective agent. [9][10][11] A serine-magnesium sulfate combination was recently proposed as an antidote for organophosphate pesticide poisoning by an ionradical mechanism. 12 This study therefore aimed to investigate the prevention of γ-radiation-induced DNA damage in human lymphocytes using a serinemagnesium sulfate mixture in comparison to N-acetylcysteine (NAC) and cysteine.…”

mentioning

confidence: 99%

Prevention of γ-Radiation-Induced DNA Damage in Human Lymphocytes Using a Serine-Magnesium Sulfate Mixture

Changizi

Bahrami

Esfahani

et al. 2017

SQUMJ

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Objectives: Ionising radiation has deleterious effects on human cells. N-acetylcysteine (NAC) and cysteine, the active metabolite of NAC, are well-known radioprotective agents. Recently, a serine-magnesium sulfate combination was proposed as an antidote for organophosphate toxicity. This study aimed to investigate the use of a serine-magnesium sulfate mixture in the prevention of γ-radiation-induced DNA damage in human lymphocytes as compared to NAC and cysteine. Methods: This study was carried out at the Iran University of Medical Sciences, Tehran, Iran, between April and September 2016. Citrated blood samples of 7 mL each were taken from 22 healthy subjects. Each sample was divided into 1 mL aliquots, with the first aliquot acting as the control while the second was exposed to 2 Gy of γ-radiation at a dose rate of 102.7 cGy/minute. The remaining aliquots were separately incubated with 600 μM concentrations each of serine, magnesium sulfate, serine-magnesium sulfate, NAC and cysteine before being exposed to 2 Gy of γ-radiation. Lymphocytes were isolated using a separation medium and methyl-thiazole-tetrazolium and comet assays were used to evaluate cell viability and DNA damage, respectively. Results: The serine-magnesium sulfate mixture significantly increased lymphocyte viability and reduced DNA damage in comparison to serine, magnesium sulfate, NAC or cysteine alone (P <0.01 each). Conclusion: The findings of the present study support the use of a serine-magnesium sulfate mixture as a new, non-toxic, potent and efficient radioprotective agent.

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“…Because of its advantages such as simplicity, reliability, validity and applicability in different cell types, the micronucleus test has been used for many years [12][13][14][15][16][17] .…”

Section: Discussionmentioning

confidence: 99%

“…The bone marrow was flushed out from both femora using 1 ml of fetal calf serum and centrifuged at 336 g for 10 min and the supernatant was discarded. Evenly spread bone marrow smears were stained using the May-Grünwald and Giemsa protocol [12] . Slides were scored at a magnification of 1000x using a light microscope.…”

Section: Micronucleus Testmentioning

confidence: 99%

Bütil Hidroksitoluen Tarafından Mikronükleus İndüksiyonunun Wistar Sıçan Kemik İliği Hücrelerinde Araştırılması

Polat¹,

Bingöl²,

Turaçlar³

2014

Kafkas Univ Vet Fak Derg

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SummaryThis study aims to investigate whether Butylated Hydroxytoluene (BHT), the synthetic antioxidant and food additive, increases the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in rat bone marrow. BHT, dissolved in corn oil, was administered intraperitoneally to 8-10 week old male and female Wistar rats (n=36) in three different doses (125, 250 and 500 mg/kg b.w.) for two different time periods. 12-and 24-h after BHT treatment, the bone marrow samples were analyzed for the frequency of MNPCEs. Additionally, by evaluating the ratio of polychromatic erythrocyte to normochromatic erythrocyte (PCE/NCE), the cytotoxic effect of BHT on bone marrow was tested. It was found that all BHT doses at two time periods significantly increased the MNPCEs frequency about 1.9-2.84 fold. On the other hand, BHT caused significant decreased in the PCE/NCE ratio, which is indicative of bone marrow cytotoxicity when compared to the control groups. This study showed that BHT increased the formation of MNPCEs in rat bone marrow and we think that this increase might be related to the applied doses and the administration way BHT. Keywords: Butylated hydroxytoluene, Cytotoxicity, Genotoxicity, Micronucleus Bütil Hidroksitoluen Tarafından Mikronükleus İndüksiyonunun Wistar Sıçan Kemik İliği Hücrelerinde Araştırılması ÖzetBu çalışma ile sentetik antioksidan ve yiyeceklerde katkı maddesi olarak kullanılan Bütil Hidroksitoluenin (BHT) rat kemik iliğinde mikronükleuslu polikromatik eritrositlerin sayılarında herhangi bir artışa neden olup olmadığı araştırıldı. Mısır yağında çözülen BHT, iki farklı zaman periyodu ve üç farklı dozda (125, 250, 500 mg/kg v.a.), 8-10 haftalık erkek ve dişi Wistar albino sıçanlara (n=36) intraperitonal olarak verildi. BHT muamelesinden 12 ve 24 saat sonra kemik iliği örnekleri MNPCE sayısı için analiz edildi. Ayrıca, polikromatik eritrositlerin normokromatik eritrositlere oranı (PCE/NCE) değerlendirilerek BHT'nin kemik iliğindeki sitotoksik etkisine bakıldı. Bütün BHT dozları ve iki farklı zaman periyodunda MNPCE'lerin sayısında 1.9-2.84 kat önemli artışlar bulundu. Diğer taraftan BHT, kemik iliği sitotoksisite belirteci olan PCE/NCE oranını kontrol grubuna kıyasla düşürdü. Sonuç olarak bu çalışmada BHT'nin rat kemik iliğinde MNPCE oluşumunu artırdığını ve bu artışın, uygulanan dozlar ve verilme şekliyle ilişkili olabileceğini düşünmekteyiz.

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Effect of N-acetylcysteine on Radiation-induced Genotoxicity and Cytotoxicity in Rat Bone Marrow

Cited by 36 publications

References 43 publications

N-acetylcysteine protects induced pluripotent stem cells from in vitro stress: impact on differentiation outcome

N-acetylcysteine protects induced pluripotent stem cells from in vitro stress: impact on differentiation outcome

Prevention of γ-Radiation-Induced DNA Damage in Human Lymphocytes Using a Serine-Magnesium Sulfate Mixture

Bütil Hidroksitoluen Tarafından Mikronükleus İndüksiyonunun Wistar Sıçan Kemik İliği Hücrelerinde Araştırılması

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