Oxidative stress and DNA damage in utero and embryo implantation of mice exposed to carbon disulfide at peri-implantation

2013 ◽  
Vol 33 (4) ◽  
pp. 424-434 ◽  
Author(s):  
L Yang ◽  
B Zhang ◽  
Y Yuan ◽  
C Li ◽  
Z Wang

Carbon disulfide (CS2) has reproductive toxicity but the mechanism remains unclear. The aim of the present study was to investigate the effect of oxidative stress and DNA damage on embryo implantation of mice exposed to CS2 at peri-implantation. CS2 exposure was on gestational day 3 (GD3), GD4, GD5 and GD6, separately, and the number of embryonic day 9 (E9) mouse embryos was obtained. DNA damage of endometrial cells, oxidative stress and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) level in uterus tissues were tested with time series at different end points after exposure. The number of E9 mouse embryos significantly decreased in all CS2 exposure groups, especially on GD4 exposure. The rates of embryo implantation decreased by 43.05%, 63.74%, 60.45% and 47.26% for CS2 exposure on GD3, GD4, GD5 and GD6, respectively. Oxidative stress significantly increased within 24 h and reached the top level at 18 h after exposure. The same time-dependent trend was observed no matter when the exposure happened at peri-implantation. 8-OH-dG significantly increased at 18 h and 24 h after exposure by 893.8% and 647.4%, respectively, when compared with the control. The indexes of DNA damage significantly increased at 6 h after exposure, which appeared earlier than the changes of oxidative stress and 8-OH-dG. Besides, both oxidative stress and DNA damage showed a strong negative correlation with the number of E9 mouse embryos. The present study illustrated that CS2 directly induced DNA damage in endometrial cells and enhanced the action through oxidative stress, both of which were responsible for CS2-induced embryo loss.

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Sinem Ilgın ◽  
Gözde Aydoğan-Kılıç ◽  
Merve Baysal ◽  
Volkan Kılıç ◽  
Mina Ardıç ◽  
...  

Depression and anxiety are recognized as public health problems. Epidemiological studies have shown that depression and anxiety often occur during reproductive ages between 20 and 60 years of age in males. Trazodone is one of the most frequently prescribed drugs in the treatment of depression and anxiety. Drugs used in repeated doses also play a role in the etiology of infertility. In our study, it was aimed to identify the possible toxic effects of trazodone on male rats and elucidate the underlying mechanisms. Vehicle or trazodone (5, 10, and 20 mg/kg/day) was administered to rats for 28 consecutive days (n=8 per group). At the end of that period, sperm concentration, motility, morphology, and DNA damage were determined and testicular morphology was assessed histopathologically in rats. Additionally, we investigated hormonal status by determining serum testosterone, FSH, and LH levels and oxidative stress by determining glutathione and malondialdehyde levels in testicular tissue to elucidate mechanisms of possible reproductive toxicity. According to our results, sperm concentration, sperm motility, and normal sperm morphology were decreased; sperm DNA damage was increased in trazodone-administered groups. Degenerative findings on the testicular structure were observed after trazodone administration in rats. Additionally, serum FSH, LH, and testosterone levels were elevated in the trazodone-administered groups. Increased MDA levels were the signs of enhanced oxidative stress after trazodone administration in testis tissues. Thus, we concluded that trazodone induced reproductive toxicity in male rats; this reproductive toxicity was accompanied by oxidative stress and hormonal changes, which are considered as important causes of reproductive disorders.


2013 ◽  
Vol 273 (2) ◽  
pp. 381-389 ◽  
Author(s):  
Bingzhen Zhang ◽  
Chunzi Shen ◽  
Liu Yang ◽  
Chunhui Li ◽  
Anji Yi ◽  
...  

2020 ◽  
Vol 71 (4) ◽  
pp. 320-328
Author(s):  
Ana Valenta Šobot ◽  
Dunja Drakulić ◽  
Gordana Joksić ◽  
Jadranka Miletić Vukajlović ◽  
Jasmina Savić ◽  
...  

AbstractYellow gentian (Gentiana lutea L.), a medicinal plant widely used in traditional medicine, displays multiple biological effects, ranging from beneficial to toxic. Since many promising applications have been reported so far, our aim was to evaluate its potential concentration- and time- dependent cytotoxic and genotoxic effects in vitro. To that end we exposed human peripheral blood mononuclear cells to 0.5, 1, and 2 mg/mL of yellow gentian root extract (YGRE) to determine its effects on oxidative stress parameters [pro/antioxidant balance (PAB) and lipid peroxidation], DNA damage (alkaline comet assay and chromosome aberrations), and cell viability (trypan blue exclusion test). Cell viability decreased with increasing concentrations and treatment duration. Only the lowest YGRE concentration (0.5 mg/mL) increased oxidative stress but produced minor DNA damage and cytotoxicity. At higher concentrations, redox parameters returned to near control values. The percentage of chromosome aberrations and percentage of DNA in the comet tail increased with increased YGRE concentration after 48 h and declined after 72 h of treatment. This points to the activation of DNA repair mechanism (homologous recombination), evidenced by the formation of chromosomal radial figures after 72 h of treatment with the highest YGRE concentration of 2 mg/mL. Our results suggest that YGRE, despite induction of cytotoxic and genotoxic effects, activates cell repair mechanisms that counter oxidative and DNA lesions and induce cell death in highly damaged cells. Therefore, observed protective effects of yellow gentian after longer exposure could be a result of activated repair and removal of cells with irreparable damage.


2016 ◽  
Vol 16 (4) ◽  
pp. 563-571 ◽  
Author(s):  
Yahya Hasan Hobani

Background. Murraya koenigii (L.) Spreng, is a significant herb of traditional Ayurvedic system of medicine. Koenimbine, a carbazole alkaloid isolated from this plant holds antiproliferative and apoptotic effects. The aim of this study was to assess koenimbine-induced DNA damage and to clarify the role of free radicals in cell death mechanisms, using HepG2 cells. Methods. The level of cytotoxicity was assayed by MTT assay. To elucidate the role of glutathione (GSH), the intracellular GSH level was analyzed. The effect of koenimbine in the cell mitochondria was evaluated using mitochondrial membrane potential (MMP) changes. Single cell gel electrophoresis assay was used to examine the level of DNA damage. Heat shock proteins, Hsp 70 and Hsp 90 expressions were checked at mRNA and protein level. Ascorbic acid and catalase were used as control antioxidants. Results. It was observed that koenimbine considerably increased DNA damage in HepG2 cells at subcytotoxic concentrations. Koenimbine induced the increased levels of reactive oxygen species (ROS) and reduction of GSH level in HepG2 cells, together with time-dependent loss of MMP. In addition, results clearly showed that koenimbine encouraged cells to express Hsp 70 and Hsp 90 in a concentration-dependent manner up to a concentration of 100 µM and a time-dependent manner at 24-hour incubation both at transcriptional and translational levels. The antioxidant capacity of ascorbic acid was found to be not as prominent as to catalase throughout the study. Conclusion. Based on these data it can be concluded that koenimbine causes DNA strand breaks in HepG2 cells, probably through oxidative stress. Moreover, the oxidative stress induced was closely associated with MMP reduction and GSH depletion associated with HSP modulation at subcytotoxic concentration.


2019 ◽  
Vol 4 (2) ◽  
pp. 46-58 ◽  
Author(s):  
Okunola A. Alabi ◽  
Lanre R. Oladimeji ◽  
Adewale A. Sorungbe ◽  
Yetunde M. Adeoluwa

AbstractIn this study, the potential DNA damage and reproductive toxicity of sorbitol was investigated using bone marrow micronucleus (MN), sperm morphology, and sperm count in mice. Five doses of 90, 45, 20, 10 and 1 mg/kg/day, defined by allometry, and approximately corresponding to 1.5g, 750mg, 330mg, 165mg and 16mg of sorbitol daily consumption by a 70kg human, respectively, were used. MN analysis showed a dose-dependent induction of micronucleated polychromatic erythrocytes and other nuclear abnormalities across the treatment groups. Assessment of sperm shape showed a significant (p < 0.05) increase in sperm abnormalities with significant (p < 0.05) decrease in mean sperm count in treated groups. The result of the oxidative stress biomarkers showed induction of significant (p < 0.05) increase in liver catalase, MDA and serum ALT and AST activities with concomitant decrease in SOD activities in exposed mice. A significant increase in weight of exposed mice were recorded when compared with the negative control. The results of this study showed the genotoxicity and reproductive effects of sorbitol.


Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.


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