MNPs-Fe3o4 Induce Leukemia Cell Apoptosis by Oxidative Stress

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4304-4304
Author(s):  
Ying Wang ◽  
Bao-An Chen ◽  
Guo-hua Xia ◽  
Ziying Jian ◽  
Zhi Li ◽  
...  

Abstract Abstract 4304 The present study evaluated on the safe concentration for normal monocyte cells whether the magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) could induce caspase3-dependent apoptosis in SKM1 cells and U937 cells by oxidative damage. The average sizes of the particles were carefully determined by transmission electron microscopy. The viability of the cells after exposed to different concentration MNPs-Fe3O4 for 12h, 24h, 48h and 72h were detected by trypan blue staining. Cell cycle after exposure for 72h was analysed by propidium iodide (PI) staining. Apoptosis of MNPs-Fe3O4 group were detected and determined by Annexin V-FITC/PI double staining, 5,5’,6,6’-tetrachloro-1, 1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) probe and Wright - Giemsa staining. ROS in SKM1 cells and U937 cells after exposure were determined by flow cytometry after dichlorofluoroescein diacetate (DCFH-DA) staining. The changes of caspase3, survivin and bcl-rambo in the cells treatment with MNPs-Fe3O4 with or wtihout trolox for 48 hours were detected by western blot analysis. The significant decreased of cell viability caused by 100 μ M MNPS-Fe3O4 exposure were observed in SKM1 cells and u937 cells, not in normal monocytes cells (p < 0.05), the exposure also induced the SKM1 cells and u937 cells G0/G1 arrest (p < 0.05). Annexin V / PI staining assay show that 100 μ M MNPs-Fe3O4 group appeared more apoptosic rate in the U937 and SKM1 cells than the control group (p < 0.05), and on the same exposed concentration the apoptotic bodies could be frequently found in the U937 and SKM1 cells, while not in normal monocyte cells by Wright - Giemsa staining. The mitochondrial membrane potential in the two kinds of cells significantly decreased after exposed 100 μ M MNPs-Fe3O4 for 24h (p < 0.05), while pretreated with antioxidants trolox, the change was allevated (p < 0.05). DCFH-DA assay show that reactive oxygen species (ROS) generation increased in 6h of exposure in SKM1 cells and U937 cells (p < 0.05). Our results also showed the particle induced caspase3-dependent apoptosis in the SKM1 cells and U937 cells, while did not in normal monocyte cells, and increasing expression of bcl-rambo and decreasing expression of survivin involve in the process. These results suggest that on the safe concentration for normal monocyte cells MNPs-Fe3O4 could induce caspase3-dependent apoptosis in SKM1 cells and U937 cells by oxidative damage, moreover, increasing expression of bcl-rambo and decreasing expression of survivin involve in the process. Disclosures: No relevant conflicts of interest to declare.

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Gwanpyo Koh ◽  
Min-Kyoung Kim ◽  
Eun-Jin Yang ◽  
Dae-Ho Lee

We compared the effects of gliclazide, an antidiabetic agent with antioxidant properties, andN-acetyl-L-cysteine (NAC), a glutathione precursor, in protecting against 2-deoxy-D-ribose- (dRib-) induced oxidative damage in HIT-T15 cells. Using trypan blue staining and flow cytometry with annexin V/PI staining, gliclazide treatment slightly reversed dRib-induced cell death and apoptosis, and NAC treatment markedly reduced both measures. Likewise, flow cytometry using DHR 123 staining showed that the levels of dRib-induced reactive oxygen species (ROS) were partially suppressed by gliclazide and completely inhibited by NAC. Using electron spin resonance spectrometry, gliclazide and NAC scavenged hydroxyl radicals generated by Fenton reaction to a similar degree in a cell-free system. NAC, but not gliclazide, completely restored the intracellular glutathione depleted by dRib using monochlorobimane fluorescence and glutathione assays. Thus, gliclazide treatment suppressed dRib-induced oxidative damage in HIT-T15 cells less than NAC did because gliclazide did not restore the intracellular glutathione content as effectively as NAC. In addition, the elevation of intracellular glutathione rather than free radical scavenging might be an important mechanism for protecting against dRib-induced oxidative damage in aβ-cell line.


Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.


2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.


2020 ◽  
Vol 20 (18) ◽  
pp. 2316-2323 ◽  
Author(s):  
Alican Kusoglu ◽  
Bakiye G. Bagca ◽  
Neslihan P.O. Ay ◽  
Guray Saydam ◽  
Cigir B. Avci

Background: Ruxolitinib is a selective JAK1/2 inhibitor approved by the FDA for myelofibrosis in 2014 and nowadays, comprehensive investigations on the potential of the agent as a targeted therapy for haematological malignancies are on the rise. In multiple myeloma which is a cancer of plasma cells, the Interleukin- 6/JAK/STAT pathway is emerging as a therapeutic target since the overactivation of the pathway is associated with poor prognosis. Objective: In this study, our purpose was to discover the potential anticancer effects of ruxolitinib in ARH-77 multiple myeloma cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. Methods: Cytotoxic effects of ruxolitinib in ARH-77 and NCI-BL 2171 cells were determined via WST-1 assay. The autophagy mechanism induced by ruxolitinib measured by detecting autophagosome formation was investigated. Apoptotic effects of ruxolitinib were analyzed with Annexin V-FITC Detection Kit and flow cytometry. We performed RT-qPCR to demonstrate the expression changes of the genes in the IL-6/JAK/STAT pathway in ARH-77 and NCI-BL 2171 cells treated with ruxolitinib. Results: We identified the IC50 values of ruxolitinib for ARH-77 and NCI-BL 2171 as 20.03 and 33.9μM at the 72nd hour, respectively. We showed that ruxolitinib induced autophagosome accumulation by 3.45 and 1.70 folds in ARH-77 and NCI-BL 2171 cells compared to the control group, respectively. Treatment with ruxolitinib decreased the expressions of IL-6, IL-18, JAK2, TYK2, and AKT genes, which play significant roles in MM pathogenesis. Conclusion: All in all, ruxolitinib is a promising agent for the regulation of the IL-6/JAK/STAT pathway and interferes with the autophagy mechanism in MM.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jun Ma ◽  
Xiankun Zeng ◽  
Min Zhou ◽  
Le Cheng ◽  
Difeng Ren

AbstractSpirulina platensis protein hydrolysates were prepared by digesting protein extracts with papain, and the hydrolysates were separated into 30, 10, and 3 kDa weights using membrane ultrafiltration. The 0–3 kDa low-molecular-weight Spirulina peptides (LMWSPs) proved the highest chemical antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, hydroxyl radical (·OH) scavenging activities and total antioxidant capacity. Cellular antioxidant ability of LMWPs fractions against 2000 μg/mL H2O2 induced oxidative damage of L02 cells were investigated. The MTT assay results displayed that LMWSPs at different concentrations (0–1000 μg/mL) had proliferation effect on the L02 cells and that treatment of the L02 cells with the 1000 μg/mL LMWSPs (0–3 kDa) significantly prevented H2O2-induced oxidative damage compared with control cells. Moreover, the 2′,7′-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe assay showed that the levels of ROS and NO were significantly lower in the experimental group that was treated with the peptides for 24 h than in the control group. Furthermore, using the corresponding kits, the treatment inhibited the reduction of SOD activity and the increase of MDA contents in the L02 cells. Therefore, LMWSPs (0–3 kDa) may have potential applications in antioxidant and liver health products.


Author(s):  
Arnaud Boudenot ◽  
stephane PALLU ◽  
Rustem UZBEKOV ◽  
Eric DOLLEANS ◽  
Hechmi Toumi ◽  
...  

The effects of treadmill interval training (IT) and free fall exercise were evaluated on bone parameters including osteocyte related characteristics. Thirty-eight 4-month-old male Wistar rats were randomly divided into a control group (C) and exercise groups: IT, 10 free fall impacts/day with a 10s (FF10) or 20s interval between drops (FF20), 5 days/week, for 9 weeks. We assessed: BMD, microarchitecture by µCT, mechanical strength by a three-point bending test, density and occupancy of the osteocyte lacunae by toluidine blue staining, osteocalcin and NTx systemic levels by ELISA, and bone tissue Sost mRNA expression by RT-PCR. NTx levels were significantly lower in exercise groups as compared to C. In exercise groups Sost mRNA expression was significantly lower than in C. Tb.N was significantly higher for IT and FF20 compared to C; Tb.Sp was significantly lower in FF10 compared to C. Both IT and FF20 were associated with higher tibial lacunar density as compared to FF10. Compared to FF10, IT fat mass was lower, while tibial osteocyte lacunae occupancy and systemic osteocalcin level were higher. All exercise modes were efficient in reducing bone resorption. Both IT and FF impact with appropriate recovery periods might be beneficial for bone health and osteocyte related characteristics. Novelty bullets: • Interval training is beneficial for bone mineral density • Exercises decreased both bone resorption and inhibition of bone formation (sost mRNA) • Longer interval recovery time favors osteocyte lacunae density


Author(s):  
Shirin Saberianpour ◽  
Mohamad H. Saeed Modaghegh ◽  
Mehdi Montazer ◽  
Mohammad M. Kamyar ◽  
Fatemeh Sadeghipour Kerman ◽  
...  

Most diabetic lower-limb amputations probably result from combinations of contributing causes rather than from unitary causes. Iron-induced damage might modulate the development of chronic diabetes complications. In this study, the relationship between tissue iron levels and polarization of macrophages in induction of angiogenesis was investigated in diabetic ulcer samples and the transitional zone of diabetic ulcers. Patients with diabetic ulcers who underwent amputation were included. The transitional zone of diabetic ulcers, from the same diabetic patients, was used as a control group. After tissue preparation, Perls Prussian blue staining and immunohistochemistry for CD11c, CD163, and CD68 markers were done. Vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), Tie2, and protein kinase B (also known as AKT) transcription of genes were measured by real-time polymerase chain reaction. For statistical analysis, we used independent samples t-test or its nonparametric equivalents, Mann–Whitney U test was used for quantitative variables, and chi-square (or Fisher's exact test) for qualitative variables. According to the results, the ratio of M2 to M1 macrophages was decreased in ulcers tissue compared to the transitional zone of diabetic ulcers. The expression of angiogenesis-related genes was increased due to hypoxia induction such as HIF and VEGF in ulcer tissue ( P < .0001), but the expression of vascular stability-related genes such as Tie2 was decreased ( P < .0001).In amputated diabetic ulcers, the polarization of macrophages is toward the classic type, but no connection was found in terms of tissue iron and help in the polarization of macrophages.


Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 805-813 ◽  
Author(s):  
Jianchang Yang ◽  
Li Chai ◽  
Chong Gao ◽  
Taylor C. Fowles ◽  
Zaida Alipio ◽  
...  

Abstract Increasing studies suggest that SALL4 may play vital roles in leukemogenesis and stem cell phenotypes. We have mapped the global gene targets of SALL4 using chromatin immunoprecipitation followed by microarray hybridization and identified more than 2000 high-confidence, SALL4-binding genes in the human acute promyelocytic leukemic cell line, NB4. Analysis of SALL4-binding sites reveals that genes involved in cell death, cancer, DNA replication/repair, and cell cycle were highly enriched (P < .05). These genes include 38 important apoptosis-inducing genes (TNF, TP53, PTEN, CARD9, CARD11, CYCS, LTA) and apoptosis-inhibiting genes (Bmi-1, BCL2, XIAP, DAD1, TEGT). Real-time polymerase chain reaction has shown that expression levels of these genes changed significantly after SALL4 knockdown, which ubiquitously led to cell apoptosis. Flow cytometry revealed that reduction of SALL4 expression in NB4 and other leukemia cell lines dramatically increased caspase-3, annexin V, and DNA fragmentation activity. Bromodeoxyuridine-incorporation assays showed decreased numbers of S-phase cells and increased numbers of G1- and G2-phase cells indicating reduced DNA synthesis, consistent with results from cell proliferation assays. In addition, NB4 cells that express low levels of SALL4 have significantly decreased tumorigenecity in immunodeficient mice. Our studies provide a foundation in the development of leukemia stem cell–specific therapy by targeting SALL4.


2020 ◽  
Vol 1 (1) ◽  
pp. 10-14
Author(s):  
Seyed Salam Kohnepoushi ◽  
Dara Dastan ◽  
Amir Nili-Ahmadabadi

Background: Pistacia atlantica kurdica has recently been shown to possess free radical scavenging ability. The current study aims to investigate the protective effect of this plant against cadmium-induced nephrotoxicity. Methods: Thirty-six rats were divided into 6 groups (6 in each), and treated as follows: group 1 received normal saline (control group), group 2 (positive control) received cadmium by drinking water (100 mg/ L/d), group 3 received 200 mg/kg of P. atlantica extract, and groups 4-6 received cadmium as well as 50, 100 and 200 mg/kg/d of P. atlantica extract (orally), respectively. After 2 weeks, oxidative damage and renal function markers were assayed by standard methods. Results: In cadmium group, a significant increase was observed in serum blood urea nitrogen (BUN) (P<0.01) and lipid peroxidation (LPO) level of renal tissue (P<0.001) and a remarkable decrease was found in total thiol molecules (TTM) of the kidney (P<0.001). Despite the decreased renal antioxidant capacity, these changes were not significant. P. atlantica extract improved the LPO, TTM, and histopathological changes in renal tissue. Conclusion: In this study, although the P. atlantica extract did not have a significant effect on cadmiuminduced renal dysfunction, it did improve the oxidative/antioxidant balance in renal tissue.


2021 ◽  
Author(s):  
Demet Cansaran Duman ◽  
Gamze Guney Eskiler ◽  
Betül Çolak ◽  
Elif Sozen Kucukkara

Abstract Lichen secondary metabolites have drawn considerable attention in recent years due to limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. After identification of the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effect through G0/G1 arrest, nuclear bleebing and the activation of particularly initiator caspases. Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further performed.


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