The Cluster [Re6Se8I6]3− Induces Low Hemolysis of Human Erythrocytes in Vitro: Protective Effect of Albumin

Rojas-Mancilla, Edgardo; Oyarce, Alexis; Verdugo, Viviana; Zheng, Zhiping; Ramírez-Tagle, Rodrigo

doi:10.3390/ijms16011728

Cited by 12 publications

(12 citation statements)

References 19 publications

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“…Experiments were independently set in the following manner: PBMC from the same healthy donor were cultured with 3% RBC from 12 SCA patients (SS-RBC) and 9 healthy controls (AA-RBC) at 37°C and 5% CO 2 , in the presence or absence of 100 lM HU (Sigma-Aldrich, Saint Louis, MO, USA) [50,52]. After 24 h, supernatants were collected and used for the detection of IL-1b (R&D Systems, Minneapolis, USA) and LTB 4 (Cayman Chemical Company, Ann Arbor, MI, USA) using ELISA kits, according to the manufacturer's instructions.…”

Section: Il-1b Leukotriene-b4 and Nitrite Production By Pbmc Culturesmentioning

confidence: 99%

Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell

et al. 2016

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This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll-like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3 (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC). TLR and NLRP3 inflammasome could contribute to the maintenance of the inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as danger signals activating these pathways. In this study, first, we evaluated TLR (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 expression in PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from healthy individuals (AA-PBMC). In the second moment, we investigated whether SS-RBC could interfere with the expression of these molecules in PBMC from healthy donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3 inflammasome expression were investigated by qPCR. IL-1β, Leukotriene-B4 (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1β were highly expressed in SS-PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase-1, IL-1β and IL-18 expression and induced IL-1β, LTB4 and nitrite production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome expression, but increased TLR2 and IL-18 expression and reduced nitrite production. In conclusion, our data suggest that TLR and inflammasome complexes may be key inducers of inflammation in SCA patients, probably through SS-RBC; also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation, indicating the need to develop new therapeutic strategies to SCA patients that act with different mechanisms of those observed for HU.

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Section: Il-1b Leukotriene-b4 and Nitrite Production By Pbmc Culturesmentioning

confidence: 99%

Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell

et al. 2016

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“…The study was approved by the local bioethics committee. Blood samples were obtained and prepared according to a protocol described before [16]. Briefly, blood samples obtained through venipuncture were anticoagulated, red blood cells were isolated by centrifugation and washed three times with phosphate-buffered saline (PBS; NaCl 150 mM, NaH 2 PO 4 1.9 mM, Na 2 HPO 4 8.1 mM, pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

“…Red blood cells (hematocrit, 1%) suspended in distilled water or PBS were considered as controls for 100% or 0% of hemolysis, respectively. Hemolysis protocol was performed as previously reported [16]. Hemolysis was determined measuring the absorbance of supernatants at 540 nm immediately or after 24 h of incubation.…”

Section: Methodsmentioning

confidence: 99%

“…The potential use of luminescent clusters in the biomedical field depends on its biological safety evaluation, including studying cellular uptake and subcellular localization, cytotoxicity, and hemolytic properties [15,16,17]. Cell uptake depends on the interaction of the cluster with the cell membranes.…”

Section: Introductionmentioning

confidence: 99%

“…To establish whether cluster administration can induce toxic effects and/or hemolysis, HepG2, EA.hy926, and human red blood cells were exposed to different doses of the cluster in vitro and evaluated for possible effects on cell viability, hemolysis, and morphological alterations [16]. Furthermore, to evaluate a potential biomedical application of the cluster, cell labelling and antiviral activity were assessed.…”

Section: Introductionmentioning

confidence: 99%

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The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

et al. 2017

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The molybdenum cluster [Mo6Cl14]2− is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of human cells and red blood cells to the molybdenum cluster and its interaction with proteins and antiviral activity in vitro. We measured cell viability of HepG2 and EA.hy926 cell lines exposed to increasing concentrations of the cluster (0.1 to 250 µM), by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Hemolysis and morphological alterations of red blood cells, obtained from healthy donors, exposed to the cluster (10 to 200 µM) at 37 °C were analyzed. Furthermore, quenching of tryptophan residues of albumin was performed. Finally, plaque formation by rotavirus SA11 in MA104 cells treated with the cluster (100 to 300 µM) were analyzed. We found that all doses of the cluster showed similar cell viability, hemolysis, and morphology values, compared to control. Quenching of tryptophan residues of albumin suggests a protein-cluster complex formation. Finally, the cluster showed antiviral activity at 300 µM. These results indicate that the cluster [Mo6Cl14]2− could be intravenously administered in animals at therapeutic doses for further in vivo studies and might be studied as an antiviral agent.

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The cluster [Re6Se8I6]3− penetrates biological membranes: drug-like properties for CNS tumor treatment and diagnosis

et al. 2018

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Tumorigenic cell lines are more susceptible to [ReSeI] cluster-induced death than normal cells, becoming a novel candidate for cancer treatment. Still, the feasibility of using this type of molecules in human patients remains unclear and further pharmacokinetics analysis is needed. Using coupled plasma optical emission spectroscopy, we determined the Re-cluster tissue content in injected mice, as a biodistribution measurement. Our results show that the Re-cluster successfully reaches different tissues, accumulating mainly in heart and liver. In order to dissect the mechanism underlying cluster biodistribution, we used three different experimental approaches. First, we evaluate the degree of lipophilicity by determining the octanol/water partition coefficient. The cluster mostly remained in the octanol fraction, with a coefficient of 1.86 ± 0.02, which indicates it could potentially cross cell membranes. Then, we measured the biological membrane penetration through a parallel artificial membrane permeability assays (PAMPA) assay. The Re-cluster crosses the artificial membrane, with a coefficient of 122 nm/s that is considered highly permeable. To evaluate a potential application of the Re-cluster in central nervous system (CNS) tumors, we analyzed the cluster's brain penetration by exposing cultured blood-brain-barrier (BBB) cells to increasing concentrations of the cluster. The Re-cluster effectively penetrates the BBB, reaching nearly 30% of the brain side after 24 h. Thus, our results indicate that the Re-cluster penetrates biological membranes reaching different target organs-most probably due to its lipophilic properties-becoming a promising anti-cancer drug with high potential for CNS cancer's diagnosis and treatment.

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The Cluster [Re6Se8I6]3− Induces Low Hemolysis of Human Erythrocytes in Vitro: Protective Effect of Albumin

Cited by 12 publications

References 19 publications

Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell

Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell

The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

The cluster [Re6Se8I6]3− penetrates biological membranes: drug-like properties for CNS tumor treatment and diagnosis

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