scholarly journals Acacia pennata L. leaves: chemical profiling and impact on DNA damage, alteration of genotoxicity—related genes expression and ROS generation in hepatic tissues of acetaminophen treated male rats

2021 ◽  
Author(s):  
Eman M. M. EL-Taher ◽  
Moshera M. El-Sherei ◽  
Riham Salah El Dine ◽  
Dina M.Y. ElNaggar ◽  
Wagdy K. B. Khalil ◽  
...  
Keyword(s):  
Dna Damage ◽  
Male Rats ◽  
Ros Generation ◽  
Chemical Profiling ◽  
Treated Male ◽  
Genes Expression

scholarly journals Design, Synthesis and Pharmacological Evaluation of Three Novel Dehydroabietyl Piperazine Dithiocarbamate Ruthenium (II) Polypyridyl Complexes as Potential Antitumor Agents: DNA Damage, Cell Cycle Arrest and Apoptosis Induction

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1453
Author(s):  
Haoran Wang ◽  
Jianhua Wei ◽  
Hong Jiang ◽  
Ye Zhang ◽  
Caina Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Antitumor Agents ◽  
Mechanistic Study ◽  
Ros Generation ◽  
Polypyridyl Complexes ◽  
Expression Levels ◽  
Cycle Arrest ◽  
Study Results

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (6a–6c) were synthesized as antitumor agents. Compounds 6a and 6c exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP. Importantly, 6a effectively inhibited tumor growth in the T-24 xenograft mouse model in comparison with cisplatin. Gel electrophoresis assay indicated that DNA was the potential targets of 6a and 6c, and the upregulation of p-H2AX confirmed this result. Cell cycle arrest studies demonstrated that 6a and 6c arrested the cell cycle at G1 phase, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of cyclin E. In addition, 6a and 6c caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-9, cytochrome c, intracellular Ca2+ release, reactive oxygen species (ROS) generation and the downregulation of Bcl-2. These mechanistic study results suggested that 6a and 6c exerted their antitumor activity by inducing DNA damage, and consequently causing G1 stage arrest and the induction of apoptosis.

CYT-Rx20 Inhibits Cervical Cancer Cell Growth and Migration Through Oxidative Stress-Induced DNA Damage, Cell Apoptosis, and Epithelial-to-Mesenchymal Transition Inhibition

2017 ◽  
Vol 27 (7) ◽  
pp. 1306-1317
Author(s):  
Yen-Yun Wang ◽  
Pei-Wen Hsieh ◽  
Yuk-Kwan Chen ◽  
Stephen Chu-Sung Hu ◽  
Ya-Ling Hsu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Cervical Cancer Cell ◽  
Ros Generation ◽  
Mesenchymal Transition ◽  
Cervical Cancer Cells

ObjectiveThe β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a β-nitrostyrene derivative CYT-Rx20 (3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene) was synthesized, and its anticancer activity on cervical cancer cells and the mechanisms involved were investigated.MethodsThe effect of CYT-Rx20 on human cervical cancer cell growth was evaluated using cell viability assay. Reactive oxygen species (ROS) generation and annexin V staining were detected by flow cytometry. The protein expression levels of cleaved caspase-3, cleaved caspase-9, cleaved poly (ADPribose) polymerase, γH2AX, β-catenin, Vimentin, and Twist were measured by Western blotting. DNA double-strand breaks were determined by γ-H2AX foci formation and neutral comet assay. Migration assay was used to determine cancer cell migration. Nude mice xenograft was used to investigate the antitumor effects of CYT-Rx20 in vivo.ResultsCYT-Rx20 induced cytotoxicity in cervical cancer cells by promoting cell apoptosis via ROS generation and DNA damage. CYT-Rx20-induced cell apoptosis, ROS generation, and DNA damage were reversed by thiol antioxidants. In addition, CYT-Rx20 inhibited cervical cancer cell migration by regulating the expression of epithelial-to-mesenchymal transition markers. In nude mice, CYT-Rx20 inhibited cervical tumor growth accompanied by increased expression of DNA damage marker γH2AX and decreased expression of mesenchymal markers β-catenin and Twist.ConclusionsCYT-Rx20 inhibits cervical cancer cells in vitro and in vivo and has the potential to be further developed into an anti-cervical cancer drug clinically.

scholarly journals Engineered Nanoparticles Induce DNA Damage in Primary Human Skin Cells, Even at Low Doses

Nano LIFE ◽  
2014 ◽  
Vol 04 (01) ◽  
pp. 1440001 ◽  
Author(s):  
Amelia A. Romoser ◽  
Michael F. Criscitiello ◽  
Christie M. Sayes
Keyword(s):  
Dna Damage ◽  
Stress Protein ◽  
Dermal Fibroblasts ◽  
Engineered Nanoparticles ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Dna Double Strand Breaks ◽  
Biological Reduction ◽  
Strand Breaks ◽  
Dna Strand

It is well documented that various particulate matter — either incidental or engineered — are known to generate reactive oxygen species (ROS) in living cells. In circumstances where these reactive species are generated, antioxidant production is often increased. This balance in the biological reduction/oxidation (a.k.a. redox) state within the cell has not been thoroughly studied in exposures involving engineered nanoparticles. However, nanoparticle exposure has been postulated to induce a DNA damage cascade. In this study, we examined primary human dermal fibroblasts (HDF) exposed to three different, but commonly used engineered nanoparticles (i.e., cerium dioxide ( CeO 2), titanium dioxide ( TiO 2) and zinc oxide ( ZnO )) in an attempt to determine the potential DNA damaging effects through the analysis of ROS generation, relevant protein upregulation response and single and double DNA strand breaks. Cell death was most elevated with exposure to ZnO , followed by TiO 2 and CeO 2. ROS generation was measured at 1 h, 6 h and 24 h after exposure to particles via a cell-based DCFH-DA (2′, 7′-dichlorfluorescein-diacetate) assay and indicated that ZnO generated the most significant amount of ROS. ZnO also caused upregulation of oxidative stress protein, heme oxygenase-1 and phosphorylation of p38; whereas CeO 2 caused upregulation of superoxide dismutase. Results from the comet assay indicated that ZnO triggered significant DNA damage in cells at relatively low dosing concentrations (20 ppm). Immunocytochemistry with ZnO -treated cells revealed notable DNA double strand breaks evidenced by a marked increase in the presence of γ-H2AX foci. This finding was also indicated by western blot, as well as cell cycle arrest by the phosphorylation of cyclin-dependent kinase 1. These data suggest that the three particle-types induce different degrees of DNA damage. And, of the three particle-types tested, exposure to ZnO nanoparticles may cause the most significant DNA damage.

ROS generation and DNA damage contribute to abamectin-induced cytotoxicity in mouse macrophage cells

Chemosphere ◽  
2019 ◽  
Vol 234 ◽  
pp. 328-337 ◽  
Author(s):  
Yiran Liang ◽  
Bizhang Dong ◽  
Nannan Pang ◽  
Jiye Hu
Keyword(s):  
Dna Damage ◽  
Ros Generation ◽  
Mouse Macrophage ◽  
Macrophage Cells

scholarly journals AMELIORATIVE EFFECTS OF GRAPE SEED OIL ON CHROMIUM-INDUCED NEPHROTOXICITY AND OXIDATIVESTRESS IN RATS

2020 ◽  
Vol 57 (3) ◽  
Author(s):  
Sahar Hassan Orabi ◽  
Sherif Mohamed Shawky
Keyword(s):  
Dna Damage ◽  
Hexavalent Chromium ◽  
Seed Oil ◽  
Potassium Dichromate ◽  
Serum Levels ◽  
Grape Seed ◽  
Renal Tissue ◽  
Male Rats ◽  
Group I ◽  
Grape Seed Oil

The current study focused on investigating the renoprotective effects of grape seed oil (GSO) against hexavalent chromium (Cr (VI))-induced nephrotoxicity. A total of 40 male rats were randomly divided into four groups: group I served as the control group, group II received 1000 mg/L potassium dichromate (353.5 mg/L Cr(VI)) in drinking water for 12 weeks, group III received 3.7 g/kg body weight/day GSO orally for 12 weeks, and group IV received GSO together with potassium dichromate for 12 weeks. Cr(VI) significantly increased serum levels of urea, creatinine, potassium and glucose. In addition, Cr(VI) increased MDA levels and induced renal tissue damage and DNA damage. On the other hand, Cr(VI) decreased serum levels of sodium and antioxidant defence system [reduced glutathione (GSH) and catalase (CAT)]. However, treatment with GSO prevented elevation levels of serum urea, creatinine, potassium and glucose. In addition, GSO enhanced sodium level, renal tissue antioxidant defense system due to its curative effect ameliorated particularly oxidative stress, renal tissue and DNA damage. In conclusion, these results demonstrate that GSO is a promising nephroprotective agent against Cr(VI)-induced nephrotoxicity.Key words: grape seed oil; hexavalent chromium; nephrotoxicity; DNA damage BLAŽILNI UČINKI OLJA GROZDNIH PEŠK PRI TOKSIČNI OBREMENITVI LEDVIC TER VPLIV NA OKSIDATIVNI STRES PODGAN, POVZROČEN S KROMOM Povzetek: Študija je bila osredotočena na proučevanje zaščitnih učinkov olja grozdnih pešk (GSO) pri toksični obremenitvi ledvic, povzročeni s heksavalentnim kromom (Cr (VI)). Štirideset samcev podgan je bilo naključno razdeljenih v štiri skupine: skupina I - kontrolna skupina, skupina II, ki je v pitni vodi 12 tednov prejemala 1000 mg/L kalijevega dikromata (353,5 mg/L Cr (VI)), skupina III, ki je peroralno 12 tednov prejemala 3,7 g/kg telesne mase/dan GSO ter skupina IV, ki je 12 tednov prejemala GSO skupaj s kalijevim dikromatom. Cr(VI) je znatno zvišal serumske ravni sečnine, kreatinina, kalija in glukoze v serumu. Poleg tega je Cr(VI) zvišal raven MDA in povzročil poškodbe ledvičnega tkiva in poškodbe DNK. Po drugi strani je Cr(VI) znižal serumsko raven natrija in antioksidativnega obrambnega sistema, zmanjšal raven glutationske peroksidaze in katalaze. Dodajanje GSO poskusnim živalim je preprečilo zvišanje ravni sečnine v serumu, kreatinina, kalija, natrija in glukoze. Poleg tega je GSO izboljšal obrambni sistem antioksidantov ledvičnega tkiva. Zaradi svojega zdravilnega učinka je izboljšal zlasti oksidativni stres, poškodbe ledvičnega tkiva in DNK. Rezultati kažejo, da je GSO obetavno zaščitno sredstvo za ledvica pri toksični obremenitvi, povzročeni s Cr(VI).Ključne besede: olje grozdnih pešk; heksavalentni krom; nefrotoksičnost; poškodba DNK

scholarly journals Biochemical and Molecular Studies on the Role of Rosemary (Rosmarinus officinalis) Extract in Reducing Liver and Kidney Toxicity Due to Etoposide in Male Rats

2019 ◽  
pp. 1-11
Author(s):  
Majd Almakhatreh ◽  
Ezar Hafez ◽  
Ehab Tousson ◽  
Ahmed Masoud
Keyword(s):  
Dna Damage ◽  
Calcium Ions ◽  
Chloride Ions ◽  
Male Rats ◽  
Control Group ◽  
Potassium Ions ◽  
Sodium Ions ◽  
Total Proteins ◽  
Kidney Toxicity ◽  
Liver And Kidney

Aims: Etoposide (Vepesid) is chemotherapeutic drugs that inhibit topoisomerase II activity and long been used for treatment of human malignancies, where it is a semi-synthetic compound derived from the plant Podophyllum peltatum. The current study was designed to investigate the possible protective effect of rosemary extract against Etoposide -induced changes in liver and kidney functions, and DNA damage in rats. Materials and Methods: A total of 50 male Wistar albino rats were divided randomly into four groups (1st group was control; 2nd group was treated with rosemary, 3rd group was received etoposide, and 4th & 5th groups was co- and post treated groups respectively). Results: The administration of Etoposide revealed a significant increase in serum ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage. In contrast; a significant decrease in albumen, total proteins, sodium ions, and calcium ions were when compared with control group. This increased in ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage was reduced after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide  (G5) for four weeks with lowest damage in G4. Also, this decreased in albumen, total proteins, sodium ions, and calcium ions was increased after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide (G5) for four weeks with lowest damage in G4. Conclusion: It could be concluded that rosemary has a promising role and it worth to be considered as a natural substance for protective the liver and kidney toxicity induced by etoposide (Vepesid) chemotherapy.

Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone antagonist-treated male rats

1995 ◽  
Vol 132 (3) ◽  
pp. 357-362 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
E Aguilar
Keyword(s):  
Gnrh Antagonist ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Gonadotropin Releasing Hormone ◽  
Male Rats ◽  
Gonadotropin Secretion ◽  
Releasing Hormone ◽  
Treated Male ◽  
Lh Secretion ◽  
Stimulating Hormone

Tena-Sempere M, Pinilla L, Aguilar E. Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone agonist-treated male rats. Eur J Endocrinol 1995;132: 357–62. ISSN 0804–4643 The pituitary component of the feedback mechanisms exerted by testicular factors on gonadotropin secretion was analyzed in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. In order to discriminate between androgens and testicular peptides, groups of males were orchidectomized (to eliminate androgens and non-androgenic testicular factors) or injected with ethylene dimethane sulfonate (EDS), a selective toxin for Leydig cells (to eliminate selectively androgens) and treated for 15 days with vehicle or the GnRH antagonist Ac-d-pClPhe-d-pClPhe-d-TrpSer-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Org.30276, 5 mg/kg/72 hours). Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured 7 and 14 days after the beginning of treatment. We found that: in males treated with GnRH antagonist, orchidectomy or EDS treatment did not induce any increase in LH secretion; and orchidectomy, but not EDS treatment, increased FSH secretion in GnRH-treated males. The present results show that negative feedback of testicular factors on LH secretion is mediated completely through changes in GnRH actions. In contrast, a part of the inhibitory action of the testis on FSH secretion is exerted directly at the pituitary level. It can be hypothesized that non-Leydig cell testicular factor(s) inputs at different levels of the hypothalamic–pituitary axis in controlling LH and FSH secretion. Manuel Tena-Sempere, Department of Physiology, Faculty of Medicine, University of Córdoba, 14004 Córdoba, Spain

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