scholarly journals Mosquito metallomics reveal copper and iron as critical factors for Plasmodium infection

2021 ◽  
Vol 15 (6) ◽  
pp. e0009509
Author(s):  
Krystal Maya-Maldonado ◽  
Victor Cardoso-Jaime ◽  
Gabriela González-Olvera ◽  
Beatriz Osorio ◽  
Benito Recio-Tótoro ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Iron Chelation ◽  
Follicular Development ◽  
Iron Chelator ◽  
White Stripe ◽  
Copper Chelation ◽  
Metal Interactions ◽  
Larval Stages ◽  
Brown Stripe

Iron and copper chelation restricts Plasmodium growth in vitro and in mammalian hosts. The parasite alters metal homeostasis in red blood cells to its favor, for example metabolizing hemoglobin to hemozoin. Metal interactions with the mosquito have not, however, been studied. Here, we describe the metallomes of Anopheles albimanus and Aedes aegypti throughout their life cycle and following a blood meal. Consistent with previous reports, we found evidence of maternal iron deposition in embryos of Ae. aegypti, but less so in An. albimanus. Sodium, potassium, iron, and copper are present at higher concentrations during larval developmental stages. Two An. albimanus phenotypes that differ in their susceptibility to Plasmodium berghei infection were studied. The susceptible white stripe (ws) phenotype was named after a dorsal white stripe apparent during larval stages 3, 4, and pupae. During larval stage 3, ws larvae accumulate more iron and copper than the resistant brown stripe (bs) phenotype counterparts. A similar increase in copper and iron accumulation was also observed in the susceptible ws, but not in the resistant bs phenotype following P. berghei infection. Feeding ws mosquitoes with extracellular iron and copper chelators before and after receiving Plasmodium-infected blood protected from infection and simultaneously affected follicular development in the case of iron chelation. Unexpectedly, the application of the iron chelator to the bs strain reverted resistance to infection. Besides a drop in iron, iron-chelated bs mosquitoes experienced a concomitant loss of copper. Thus, the effect of metal chelation on P. berghei infectivity was strain-specific.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation

2020 ◽  
Author(s):  
Andrea Pagani ◽  
B Manuela Kirsch ◽  
Ursula Hopfner ◽  
Matthias M Aitzetmueller ◽  
Elizabeth A Brett ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Survival Rates ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Dermal Fibroblasts ◽  
Topical Formulation

Abstract Background Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. Objectives The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. Methods We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. Results In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. Conclusions The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

scholarly journals Efficacy of monepantel against lower developmental stages of a multi-resistant and susceptible Haemonchus contortus isolates: an in vitro study

2013 ◽  
Vol 50 (2) ◽  
pp. 91-95 ◽  
Author(s):  
L. Lecová ◽  
L. Stuchlíková ◽  
J. Lamka ◽  
M. Špulák ◽  
M. Várady ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Developmental Stages ◽  
In Vitro Study ◽  
Lethal Concentration ◽  
In Vitro Tests ◽  
High Efficacy ◽  
Larval Stages ◽  
New Class ◽  
Ovicidal Effect

AbstractMonepantel (MOP) belongs to a new class of anthelmintic compounds, the amino-acetonitrile derivates, which have a different mode of action as the currently used anthelmintics. Many present studies confirmed the high efficacy of MOP against fourth larval and adult stages of Haemonchus contortus. The objective of this study was to determine in vitro efficacy of MOP against lower development stages (eggs, L1–L3 larvae) and to compare it between resistant and susceptible isolates of H. contortus. For this purpose, two in vitro tests - egg hatch test and micro-agar larval development test were used. Results were quantified as 50 % lethal concentration (LC50), 99 % lethal concentration (LC99) and resistance factor (RF). This study revealed the high efficacy against lower larval stages (L1–L3) of both resistant and susceptible strains of this parasite. Larval susceptibility was not dependent of the sensitivity status of the nematode isolate. On the other hand, ovicidal effect of MOP was very low.

scholarly journals Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Mario Caruffo ◽  
Dinka Mandakovic ◽  
Madelaine Mejías ◽  
Ignacio Chávez-Báez ◽  
Pablo Salgado ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Host Cells ◽  
Bacterial Disease ◽  
Protective Capacity ◽  
Intracellular Iron ◽  
Piscirickettsia Salmonis

Abstract Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.

In vitro effect of ivermectin on Pseudoterranova decipiens survival

1989 ◽  
Vol 63 (1) ◽  
pp. 72-74 ◽  
Author(s):  
K. M. Manley ◽  
J. A. Embil
Keyword(s):  
Broad Spectrum ◽  
Developmental Stages ◽  
Culture Media ◽  
Halichoerus Grypus ◽  
Grey Seal ◽  
Larval Stages ◽  
Pseudoterranova Decipiens ◽  
Vitro Effect ◽  
Drug Vehicle

ABSTRACTThird larval stages (L3) removed from fish fillets, fourth larval stages (L4) raised in in vitro culture, and adults of Pseudoterranova decipiens, collected from grey seal (Halichoerus grypus) stomachs, were exposed to the broad spectrum anthelmintic, ivermectin. L3 and L4 parasites were exposed, in vitro, to 500, 100, 50, 20, 5 and 1 μg/ml concentrations of the drug, in culture media. Adult P. decipiens were exposed in vitro to a concentration of 500 μg/ml ivermectin, only. Controls consisted of parasites placed in culture media alone or culture media plus drug vehicle. These three developmental stages of P. decipiens were all found to be susceptible to the effects of ivermectin.

scholarly journals Oligochitosan Synthesized by Cunninghamella elegans, a Fungus from Caatinga (The Brazilian Savanna) Is a Better Antioxidant than Animal Chitosan

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 171
Author(s):  
Weslley Souza Paiva ◽  
Francisco Ernesto de Souza Neto ◽  
Moacir Fernandes Queiroz ◽  
Lucas Alighieri Neves Costa Batista ◽  
Hugo Alexandre Oliveira Rocha ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Radical Scavenging ◽  
Iron Chelation ◽  
Reducing Power ◽  
Drug Carriers ◽  
Brazilian Savanna ◽  
Cunninghamella Elegans ◽  
In Vitro Test ◽  
Copper Chelation

Animal chitosan (Chit-A) is gaining more acceptance in daily activities. It is used in a range of products from food supplements for weight loss to even raw materials for producing nanoparticles and hydrogel drug carriers; however, it has low antioxidant activity. Fungal oligochitosan (OChit-F) was identified as a potential substitute for Chit-A. Cunninghamella elegans is a fungus found in the Brazilian savanna (Caatinga) that produces OligoChit-F, which is a relatively poorly studied compound. In this study, 4 kDa OChit-F with a 76% deacetylation degree was extracted from C. elegans. OChit-F showed antioxidant activity similar to that of Chit-A in only one in vitro test (copper chelation) but exhibited higher activity than that of Chit-A in three other tests (reducing power, hydroxyl radical scavenging, and iron chelation). These results indicate that OChit-F is a better antioxidant than Chit-A. In addition, Chit-A significantly increased the formation of calcium oxalate crystals in vitro, particularly those of the monohydrate (COM) type; however, OChit-F had no effect on this process in vitro. In summary, OChit-F had higher antioxidant activity than Chit-A and did not induce the formation of CaOx crystals. Thus, OChit-F can be used as a Chit-A substitute in applications affected by oxidative stress.

Abstract 15100: A Decrease in Mitochondrial, but Not Cytosolic, Iron Protects Against Cardiac Ischemia-Reperfusion Damage Through a Reduction in ROS

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hsiang-Chun Chang ◽  
Rongxue Wu ◽  
Meng Shang ◽  
Hossein Ardehali
Keyword(s):  
Cardiac Function ◽  
Ischemia Reperfusion ◽  
Iron Chelation ◽  
Selective Reduction ◽  
Iron Chelator ◽  
Iron Chelators ◽  
Causative Role ◽  
Novel Approach ◽  
Mitochondrial Iron

Introduction: Iron can catalyze the formation of reactive oxygen species (ROS) and promote tissue damage. While some studies suggested benefits with iron chelation therapy in ischemic heart disease (IHD), several others failed to show any benefits. Mitochondria are a major site of iron utilization and ROS production, and mitochondrial iron accumulation has been associated with increased oxidative stress. We therefore hypothesized that mitochondrial iron plays a causative role in ischemia/reperfusion (I/R) damage, and a decrease in mitochondrial iron (as opposed to cytoplasmic iron) would be sufficient to protect against I/R injury. Results: We observed an increase in cardiac mitochondrial iron in mice after I/R injury. Using two iron chelators with distinct mitochondrial permeability, i.e., 2,2’-bipyridyl (BPD, a mitochondria-accessible iron chelator) and deferoxamine (DFO, an iron chelator that does not modulate mitochondrial iron), we demonstrated that mice pretreated with BPD but not DFO were protected against I/R injury. Similar results were obtained in vitro . Since these two iron chelators also modulate iron in other subcellular compartments, we used transgenic (TG) mice with cardiomyocyte-specific overexpression of the mitochondrial iron export protein ATP-binding cassette (ABC)-B8 to confirm that modulation of mitochondrial iron alone is sufficient to confer protection. ABCB8 TG mice had significantly lower mitochondrial iron (but normal cytosolic iron) in the heart compared to nontransgenic (NTG) littermates at baseline, but exhibited normal cardiac function. After I/R, ABCB8 TG mice displayed significantly less apoptosis and lower levels of markers of ROS and better preserved cardiac function than NTG littermates, suggesting that a reduction in mitochondrial iron protects against I/R injury, most likely through a reduction in ROS. Conclusions: Our findings demonstrate that selective reduction in mitochondrial iron is sufficient to protect against I/R injury. Thus, targeting mitochondrial iron with selective iron chelators may provide a novel approach for the treatment of IHD.

Effects of Iron Chelation in Osteosarcoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Maura Argenziano ◽  
Alessandra Di Paola ◽  
Chiara Tortora ◽  
Daniela Di Pinto ◽  
Elvira Pota ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Background: Osteosarcoma is an aggressive bone tumor. Itrepresents the principal cause of cancer-associated death in children.Considering the recent findings on the role of iron in cancer, iron chelation has been investigated for its antineoplastic properties in many tumors. Deferasirox is the most used iron chelator compound and in previous studies showed an anticancer effectinhematologic and solid malignancies. Eltrombopag is a Thrombopoietin receptor used in thrombocytopenia, that also binds and mobilize iron. It demonstrated an effect in iron overload conditions and also in contrasting cancer cells proliferation. Objective: We analyzed the effects of Deferasirox and Eltrombopag in Human Osteosarcoma cells, in the attempt to identify other therapeutic approaches for this tumor. Methods: We cultured and treated withDeferasirox and Eltrombopag, alone and in combination, two human osteosarcoma cell lines, MG63 and 143B. After 72h exposure, we performed RTqPCR, Western Blotting, Iron Assay and cytofluorimetric assays to evaluate the effect on viability, apoptosis, cell cycle progression and ROS production. Results: The iron chelating properties of the two compounds are confirmed also in Osteosarcoma, but we did not observe any direct effect on tumor progression. Discussion: We tested Deferasirox and Eltrombopag, alone and in combination, in Human Osteosarcoma cells for the first time and demonstrated that their iron chelating activity does not influence biochemical pathways related to cancer progression and maintenance. Conclusion: Although further investigations on possible effects mediated by cells of the tumor microenvironment could be of great interest, in vitro iron chelation in Osteosarcoma does not impair tumor progression.

Functional effects of Tribbles homolog 2 in bovine ovarian granulosa cells†

2020 ◽  
Vol 102 (6) ◽  
pp. 1177-1190
Author(s):  
Aly Warma ◽  
Kalidou Ndiaye
Keyword(s):  
Western Blot ◽  
Granulosa Cells ◽  
Developmental Stages ◽  
Polyclonal Antibodies ◽  
Differentially Expressed Gene ◽  
Follicular Development ◽  
Mapk Signaling ◽  
Tissue Growth ◽  
Ovulatory Follicles

Abstract Tribbles homologs (TRIB) 1, 2, and 3 represent atypical members of the serine/threonine kinase superfamily. We previously identified TRIB2 as a differentially expressed gene in granulosa cells (GCs) of bovine preovulatory follicles. The current study aimed to further investigate TRIB2 regulation and study its function in the ovary. GCs were collected from follicles at different developmental stages: small antral follicles (SF), dominant follicles (DF) at day 5 of the estrous cycle, and hCG-induced ovulatory follicles (OFs). RT-qPCR analyses showed greater expression of TRIB2 in GC of DF as compared to OF and a significant downregulation of TRIB2 steady-state mRNA amounts by hCG/LH, starting at 6 h through 24 h post-hCG as compared to 0 h. Specific anti-TRIB2 polyclonal antibodies were generated and western blot analysis confirmed TRIB2 downregulation by hCG at the protein level. In vitro studies showed that FSH stimulates TRIB2 expression in GC. Inhibition of TRIB2 using CRISPR/Cas9 resulted in a significant increase in PCNA expression and an increase in steroidogenic enzyme CYP19A1 expression, while TRIB2 overexpression tended to decrease GC proliferation. TRIB2 inhibition also resulted in a decrease in transcription factors connective tissue growth factor (CTGF) and ankyrin repeat domain-containing protein 1 (ANKRD1) expression, while TRIB2 overexpression increased CTGF and ANKRD1. Additionally, western blot analyses showed reduction in ERK1/2 (MAPK3/1) and p38MAPK (MAPK14) phosphorylation levels following TRIB2 inhibition, while TRIB2 overexpression increased p-ERK1/2 and p-p38MAPK. These results provide evidence that TRIB2 modulates MAPK signaling in GC and that TRIB2 could act as a regulator of GC proliferation and function, which could affect steroidogenesis during follicular development.

scholarly journals Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 641-649 ◽  
Author(s):  
Inger B Carlsson ◽  
Mika P E Laitinen ◽  
Jennifer E Scott ◽  
Henna Louhio ◽  
Louiza Velentzis ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Developmental Stages ◽  
Culture Media ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Kit Ligand ◽  
Kit Receptor ◽  
Ovarian Follicular Development

The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell factor, SCF), are involved in ovarian follicular development in several animal species. We studied the expression of KL and c-Kit usingin situhybridization and immunohistochemistry in donated human ovarian cortical tissue. The KL transcripts were expressed in granulosa cells of primary follicles, whereas the expression of c-Kit was confined to the oocyte and granulosa cells in primary and secondary follicles. We employed an ovarian organ culture using firstly serum-containing and then serum-free medium to study the effects of KL and an anti-c-Kit antibody, ACK2, on the development and survival of ovarian folliclesin vitro. Culture of ovarian cortical slices for 7 days resulted in a 37% increase in the number of primary follicles and a 6% increase in secondary follicles. The proportion of viable follicles decreased in all cultures. The addition of KL (1, 10 and 100 ng/ml) into the culture media did not affect the developmental stages of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800 ng/ml) in the culture medium significantly increased the proportion of atretic follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of culture. In conclusion, c-Kit and KL are expressed in human ovaries during follicular development. Blocking the c-Kit receptor induces follicular atresia. The KL/c-Kit signaling system is likely to control the survival of human ovarian follicles during early follicular development.

scholarly journals Dynamic characteristics of lipid metabolism in cultured granulosa cells from geese follicles at different developmental stages

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Shanyan Gao ◽  
Xiang Gan ◽  
Hua He ◽  
Shenqiang Hu ◽  
Yan Deng ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Granulosa Cells ◽  
Dynamic Characteristics ◽  
Developmental Stages ◽  
Lipid Synthesis ◽  
Follicular Development ◽  
Vital Role ◽  
Intracellular Lipids ◽  
Expression Of Genes

Abstract Previous studies have shown that lipid metabolism in granulosa cells (GCs) plays a vital role during mammalian ovarian follicular development. However, little research has been done on lipid metabolism in avian follicular GCs. The goal of the present study was to investigate the dynamic characteristics of lipid metabolism in GCs from geese pre-hierarchical (6–10 mm) and hierarchical (F4-F2 and F1) follicles during a 6-day period of in vitro culture. Oil red O staining showed that with the increasing incubation time, the amount of lipids accumulated in three cohorts of GCs increased gradually, reached the maxima after 96 h of culture, and then decreased. Moreover, the lipid content varied among these three cohorts, with the highest in F1 GCs. The qPCR results showed genes related to lipid synthesis and oxidation were highest expressed in pre-hierarchical GCs, while those related to lipid transport and deposition were highest expressed in hierarchical GCs. These results suggested that the amount of intracellular lipids in GCs increases with both the follicular diameter and culture time, which is accompanied by significant changes in expression of genes related to lipid metabolism. Therefore, it is postulated that the lipid accumulation capacity of geese GCs depends on the stage of follicle development and is finely regulated by the differential expression of genes related to lipid metabolism.

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