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The transcriptomic response to albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) in the C. elegans strain CB3474 ben-1(e1880)III

ABSTRACT: We have undertaken a detailed analysis of the biotransformation of five of the most therapeutically important benzimidazole anthelmintics - albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) - in Caenorhabditis elegans. As a step to identifying nematode enzymes potentially responsible for benzimidazole biotransformation, we characterised the transcriptomic response to each of the benzimidazole drugs using the C. elegans strain CB3474 ben-1(e1880)III in order to minimize general phenotypic and stress responses to the drug. In the case of albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), and oxfendazole (OxBZ) - the shared transcriptomic response was dominated by the up- regulation classical xenobiotic response genes.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE130466 | GEO | 2019/04/30

REPOSITORIES: GEO

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The transcriptomic response to albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) in the C. elegans strain CB3474 ben-1(e1880)III

Project description:The transcriptomic response to albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) in the C. elegans strain CB3474 ben-1(e1880)III

| PRJNA540299 | ENA

Expression data from Caenorhabditis elegans exposed to albendazole

Project description:We have investigated how the model nematode Caenorhabditis elegans responds to and metabolizes albendazole; an important anthelmintic for human and animal parasite control. The transcriptional response of the mutant strain CB3474 ben-1(e1880)III, which is highly resistant to benzimidazoles due to a null mutation in the Î²-tubulin drug target, was examined. This approach was successful in minimizing transcriptional responses associated with non-specific stress or with the drug mode of action, resulting in only in a small subset of genes showing differential expression in response to drug exposure. Matched cultures of synchronised C. elegans were grown to young adult stage in liquid culture. The nematodes were then exposed to 300 ug/ml albendazole (ABZ) or exposed only to the DMSO excipient used to deliver the albendazole (CONT) for 4 hours. RNA was extracted from three biological replicates and hybridised to Affymetrix arrays.

2010-06-23 | E-GEOD-21747 | biostudies-arrayexpress

Expression data from Caenorhabditis elegans exposed to albendazole

2010-06-14 | GSE21747 | GEO

DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina

Project description:Intestinal helminths cause iron-deficiency anemia in pregnant women, associated with premature delivery, low birth weight, maternal ill health, and maternal death. Although benzimidazole compounds such as mebendazole (MBZ) are highly efficacious against helminths, there are limited data on its use during pregnancy. In this study, we performed in vivo imaging of the retinas of zebrafish larvae exposed to MBZ, and found that exposure to MBZ during 2 and 3 days post-fertilization caused malformation of the retinal layers. To identify the molecular mechanism underlying the developmental toxicity of MBZ, we performed transcriptome analysis of zebrafish eyes. The analysis revealed that the DNA damage response was involved in the developmental toxicity of MBZ. We were also able to demonstrate that inhibition of ATM significantly attenuated the apoptosis induced by MBZ in the zebrafish retina. These results suggest that MBZ causes developmental toxicity in the zebrafish retina at least partly by activating the DNA damage response, including ATM signaling, providing a potential adverse outcome pathway in the developmental toxicity of MBZ in mammals.

2016-03-24 | GSE75245 | GEO

RNA-seq analysis of Arabidopsis root with MBZ treatment

Project description:we reported the identification of a small molecule, Mebendazole (MBZ) that modulates GSA in Arabidopsis thaliana roots. To identify pathways immediately response to MBZ, we performed an mRNA-seq using roots of 14-days-old Arabidopsis grown on DMSO plates treated with DMSO or 10 µM MBZ for 4 hours. Differenetial expressed genes between DMSO and MBZ_4h treatments were analyzed. It has 8 samples in total, with 4 replicates for each treatment.

2022-04-29 | GSE201648 | GEO

Albendazole induces monocytic differentiation in AML cells through modulating KLF4-DPYSL2A axis

Project description:To compare the global gene expressions between KLF4-expressed AML cells and albendazole-treated AML cells, we conducted gene expression arrays in THP-1 cells lentivirally-transduced with doxycycline-inducible KLF4 or in THP-1 cells treated with albendazole in different concentrations. We identified that albendazole induces prominent differentiation in THP-1 cells through up-regulating KLF4 and DPYSL2A expressions. Considering the guaranteed safety and tolerability of albendazole in humans, this drug could easily be repositioned to AML patients once its anti-tumor efficacy is clarified.

2021-03-09 | GSE101784 | GEO

Transcriptional profiling of DNA damage tolerant (DDT) lymphomas after treatment either with Albendazole, Ethidium bromide or DMSO as a control

Project description:We studied the role of Albendazole in inducing loss of heterozygosity. Here, we generated RNA-seq data from DDT lymphomas after 12 hours of treatment either with Albendazole (400nM), Ethidium bromode (400 nM) or DMSO as a control.

2021-02-05 | GSE163419 | GEO

Application of a 9k-cDNA microarray for identification of albendazole and artemisinin targeting genes in Echinococcus granulosus larval protoscoleces

Project description:A cDNA microarray composed of 9065 uniEST probes was constructed and applied to detect the gene expression profile of protoscoleces of E. granulosus treated with albendazole and artemisinin in vitro, respectively. Compared with the untreated parasite, 7 genes were up-regulated and 38 genes were down-regulated in protoscoleces treated with albendazole and 100 genes were up-regulated and 6 genes were down-regulated in protoscoleces treated with artemisinin. The differential expression genes in protoscoleces induced by albendazole were clustered into energy metabolism, cell cycle and assembly of cell structure. And the differential expression genes affected by artemisinin were clustered into genetic information, the transduction of environmental signals, metabolism. Under transmission electron microscope observation, albendazole intervention damaged the cell structure, and form the heterochromatin in protoscoleces cells was mainly increased in the artemisinin group. Isolated E. granulosus protoscoleces were treated with albendazole and artemisinin respectively and was extracted of total RNA using the TRIZOL Reagent according to the manufacturer's instructions. Gene-expression profiling was performed for each RNA sample separately on the GeneChip of Echinococcus granulosus Genome Array (Capitalbio) at CapitalBio Corporation (Beijing, China).

2014-06-03 | E-GEOD-58136 | biostudies-arrayexpress

Application of a 9k-cDNA microarray for identification of albendazole and artemisinin targeting genes in Echinococcus granulosus larval protoscoleces

2014-06-03 | GSE58136 | GEO

Mebendazole Inhibits Histoplasma capsulatum In Vitro Growth and Decreases Mitochondrion and Cytoskeleton Protein Levels

Project description:Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum. Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum. These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment.

2023-03-22 | PXD033762 | Pride

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