scholarly journals Protective effect of resveratrol against hexavalent chromium-induced genotoxic damage in Hsd:ICR male mice

Author(s):  
Tonancy Nicolás-Méndez ◽  
Sam Kacew ◽  
Alda Rocío Ortiz-Muñiz ◽  
Víctor Manuel Mendoza-Núñez ◽  
María del Carmen García-Rodríguez

Abstract It is well-established that exposure to hexavalent chromium [Cr(VI)] induces genotoxic damage. The aim of this study was to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as possible pathways that may be associated with this protection. Hsd:ICR male mice were divided into groups of 5 each and treated as follows: a) control 1, distilled water; b) control 2, ethanol 30%; c) resveratrol, 50 mg/kg by gavage; d) CrO3, 20 mg/kg intraperitoneally; and e) resveratrol in addition to CrO3 (resveratrol+CrO3), with resveratrol administered 4 hr prior to CrO3. The frequency of micronuclei (MN) and cytotoxicity were measured in peripheral blood at 0, 24, 48 and 72 hr, while 8-hydroxydeoxyguanosine (8-OHdG, 7,8-dihydro-8-oxodeoxyguanosine) adduct repair levels, endogenous antioxidant system biomarkers and apoptosis at 48 hr after treatments. Resveratrol administration increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). CrO3 treatment elevated GPx and CAT activities. Resveratrol reduced the frequency of Cr(VI)-induced rise in MN and without significant effect on levels of 8-OHdG adduct when administered alone, suggesting that this polyphenol-mediated cellular repair does not involve 8-OHdG adduct formation. Concomitant administration of resveratrol and Cr(VI)-resulted in return of activities of SOD, GPx and CAT to control levels accompanied by decreased glutathione levels suggesting that the endogenous antioxidant system might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant toxicity. The increase in apoptotic cell number in resveratrol+CrO3 group as well as diminished necrosis further affirms that resveratrol effectively blocked the actions of Cr(VI).

Author(s):  
Ana C. Quevedo ◽  
Iseult Lynch ◽  
Eugenia Valsami-Jones

The dynamic interplay between toxicity pathways (oxidative stress, calcium disturbances, genetic damage) caused by nanoparticles and the repair mechanisms of inhibition of cell division and induction of cell death is explored in zebrafish embryo cells.


Nanoscale ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 3855-3863 ◽  
Author(s):  
Namrata Singh ◽  
Mohammed Azharuddin Savanur ◽  
Shubhi Srivastava ◽  
Patrick D'Silva ◽  
Govindasamy Mugesh

Multi-enzyme mimetic Mn3O4 nanoflowers (Mp) modulate the redox state of mammalian cells without altering the cellular antioxidant machinery under oxidative stress conditions.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Dolati ◽  
M J Zamiri ◽  
A Akhlaghi ◽  
Z Jahromi

Abstract Study question Does quercetin (75 or 100 mg/kg BW/day) co-administration with lead acetate to male mice affects embryonic development in female mice? Summary answer The low-dose quercetin (75 mg/kg BW/day) ameliorated the adverse effects of lead acetate on mouse embryogenesis. What is known already Lead causes male infertility by impacting on endocrine system and spermatogenesis, and may exert undesirable effects on the offspring. The currently approved treatment for lead poisoning is the use of chelating agents, which form an insoluble complex with lead and shield it from biological targets; thus, reducing its toxicity. One of the main mechanisms of lead-induced toxicity is oxidative stress, and it has been reported that natural antioxidants can reduce the heavy metals toxicity. The aim of the present study was to examine the protective effects of quercetin on the toxicity induced by lead acetate on the embryogenesis in mice. Study design, size, duration Sexually mature (eight-week-old) NMRI male mice (n = 24) were randomly divided into four groups (n = 6 per group) receiving (i) distilled water (control group); (ii) lead acetate (150 mg/kg BW/day) dissolved in deionized water (LA); (iii) lead acetate (150 mg/kg BW/day) + quercetin (75 mg/kg BW/day) (LQ75); (IV) lead acetate (150 mg/kg BW/day) + quercetin (100 mg/kg BW/day) (LQ100). Treatments were applied daily as oral gavages for one cycle of the seminiferous epithelium (35 days). Participants/materials, setting, methods At the end of treatment administration, the males were joined with super-ovulated females, and the retrieved zygotes were cultured for evaluation of the embryo development (at 2-cell, 4-cell, 8-cell, and blastocyst stages), and blastocyst cell number using differential staining (propidium iodide and bisbenzimide). After incubation of capacitated sperm with oocytes, an ultraviolet light microscope was used following 3 min incubation with 25 µg⁄mL bisbenzamide solution for fertilization assessment. Main results and the role of chance Lead acetate (LA) treatment of male mice decreased the 2-cell stage compared with the control group (P > 0.05). There was no difference between control and LQ75, and between LA and LQ100. The other stages of embryonic development were not significantly affected by the treatment. Overall, early embryonic development in the control and LQ75 mice were better than LQ100 and LA mice. The number of cells in the trophectoderm and inner-cell mass were not affected by treatments. However, the total blastocyst cell number in the control was higher than in the other groups; there was no significant difference between LQ100, LQ75 and LA groups. Fertilization rate was not affected by the treatments (P < 0.05). Quercetin acts as a potent antioxidant at low doses, but at high doses exerts a pro-oxidant action. According to previous reports, higher concentrations of quercetin increased apoptosis and necrosis while decreasing the activities of the antioxidant enzymes. Also, it has been suggested that quercetin might disrupt the endocrine system and interfere with Sertoli cell function and sperm motility. Limitations, reasons for caution A limitation of this study is narrow dose selection; more studies are needed to determine the effective dose of quercetin in ameliorating the lead toxicity. There are also side effects of lead-quercetin chelates such as metal redistribution, essential metal loss, accumulation and persistency in intracellular sites, and peroxidation. Wider implications of the findings: Lead administration adversely impacted on the embryogenesis; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on mice embryogenesis. Trial registration number Not applicable


2014 ◽  
Vol 229 (1) ◽  
pp. 319-326 ◽  
Author(s):  
Yang Li ◽  
Ping Li ◽  
Shanfa Yu ◽  
Ji Zhang ◽  
Tiancheng Wang ◽  
...  

2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.


2007 ◽  
Vol 19 (1) ◽  
pp. 283
Author(s):  
J. I. Park ◽  
Y. Jang ◽  
E. S. Lee

Oxidative stress is known to induce apoptotic cell death by reactive oxygen species (ROS) generated from in vitro culture systems. This study was conducted to evaluate the effect of Vitamin E (VitE), as antioxidant, on development of bovine embryos activated in vitro. Bovine ovaries were collected from slaughtered cows at a local abattoir. Oocytes were aspirated from follicles 3-8 mm in diameter and transferred to maturation medium: tissue culture medium (TCM)-199 supplemented with 10% (v/v) fetal calf serum, 100 mg/mL-1 l-cysteine, 20 mg/mL-1 sodium pyruvate, gonadotropins (250 IU each of eCG and hCG/mL), 10 mg/mL-1 epidermal growth factor, and 100 �M VitE. Oocytes were cultured at 38.9�C in 5% CO2 in humidified air. After 22 hours of culture, oocytes with polar bodies were selected and subjected to activation treatments. Oocytes were exposed to calcium ionomycin (5 �M for 5 min), followed by incubation with 6-DMAP (2 mM) for 3.5 hours in medium supplemented with or without VitE (100 �M). After activation, oocytes were cultured in mSOF medium containing 0.8% BSA at 38.9�C in 5% CO2, 5% O2 in humidified air for 7–8 days. Cell numbers were counted by the number of nuclei of blastocysts stained with Hoechst 33342, and apoptosis was detected by TUNEL assay using a MK500 kit (Takara Bio, Inc., Otsu, Shiga, Japan). Total cell and apoptotic cell number were determined under a fluorescence microscope. Data were analyzed using Student's t-test and chi-square test. The cleavage and blastocyst rates were significantly higher (P < 0.05) after activation with VitE (78.1% and 16.3%, n = 80) than without VitE (66.7% and 11.0%, n = 60). Total cell numbers were also significantly higher (P < 0.05) in blastocysts after activation with VitE (143.0 ± 34.02, n = 21) than in those without VitE (127.63 ± 40.25, n = 20). However, the percentage of TUNEL-positive (apoptotic) cells was similar between blastocysts activated with VitE (5.38 ± 2.22) and those without VitE (6.76 ± 1.98). The results of the present study demonstrate that vitamin E added to activation medium promoted further development of activated embryos, although its role in the alleviation of apoptosis remains unclear.


2020 ◽  
Vol 21 (14) ◽  
pp. 4976
Author(s):  
Wan Seok Kang ◽  
Hakjoon Choi ◽  
Goeun Jang ◽  
Ki Hoon Lee ◽  
Eun Kim ◽  
...  

We investigated the time-dependent deleterious ocular changes induced by urban particulate matter (UPM) in vitro and in vivo. UPM treatment decreased human corneal epithelial cell migration and survival. Fluorescein scores were consistently increased by UPM application for 16 weeks. One week of rest at 2 or 4 weeks led to a recovery trend, whereas two weeks of rest at 8 weeks induced no change. UPM treatment decreased the tear film break-up time at 2 weeks, which was thereafter maintained until 16 weeks. No changes were found after periods of rest. UPM-treated eyes exhibited greater corneal epithelium thickness than normal eyes at 2 weeks, which recovered to normal at 4 and 8 weeks and was significantly decreased at 16 weeks. Apoptotic cell number in the epithelium was increased at 2 weeks, which remained constant except at 8 weeks. IL-6 expression in the cornea of the right eye continually increased for 16 weeks, and significant recovery was only observed at 8 weeks after 2 weeks of rest. Ocular pressure was significantly increased in the right eye at 12 and 16 weeks. Topical UPM application to the eye induced deleterious changes to various closely related parts of the eye.


2018 ◽  
Vol 17 (4) ◽  
pp. 317-322
Author(s):  
Morgan B. Giers ◽  
Liudmila Bardonova ◽  
Kyle Eyster ◽  
Vadim Byvaltsev ◽  
Mark C. Preul

ABSTRACT Introduction: Apoptosis is a contributing factor to degenerating intervertebral disc (IVD). Disc regeneration has been attempted by transplanting cells into the disc, with some gains in disc height achieved in animal models. Here, we study whether the apoptotic microenvironment affects the transplanted disc cells. Methods: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were grown in media then starved for 5 days in vitro by not changing the media. Three aspects of apoptotic cell influence on the transplanted cells were tested in a total of 32 samples: 1) the effect of apoptotic cytokines in the media, 2) reduced glucose in the media, and 3) apoptotic cell bodies in the flask. The Trypan Blue, AlamarBlue®, and 1,9-Dimethyl-Methylene Blue assays for sulfated glycosaminoglycan (sGAG) content were performed (n=4). Results: There were significant decreases in cell viability between the control, 25% conditioned media (CM) and starved control group. There were no significant differences in cell number, metabolic activity or sGAG production in cells grown in different conditioned media compared to cells grown in complete media. The cells of the control decreased in viability and number over the 5 days without feeding, then improved dramatically when feeding was resumed. Flasks that received transplanted cells in addition to renewed feeding did not recover as much as the cells in the re-fed group. Conclusions: Cytokines from starved cells negatively impact on the viability of healthy cells. Starving cells that receive new sources of nutrition have even higher viability than transplanted cells. This indicates that altering and improving the nutrient supply problem in the IVD could be a valuable option. Level of Evidence III; Case control studyg.


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