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Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney

Gyps species have been previously shown to be highly sensitive to the toxic effects of diclofenac, when present in their food sources as drug residues following use as a veterinary medicine. Vultures exposed to diclofenac soon become depressed and die with signs of severe visceral gout and renal dam...

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Autores principales: Nethathe, Bono, Phaswane, Rephima, Abera, Aron, Naidoo, Vinny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096082/
https://www.ncbi.nlm.nih.gov/pubmed/33945567
http://dx.doi.org/10.1371/journal.pone.0250408
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author Nethathe, Bono
Phaswane, Rephima
Abera, Aron
Naidoo, Vinny
author_facet Nethathe, Bono
Phaswane, Rephima
Abera, Aron
Naidoo, Vinny
author_sort Nethathe, Bono
collection PubMed
description Gyps species have been previously shown to be highly sensitive to the toxic effects of diclofenac, when present in their food sources as drug residues following use as a veterinary medicine. Vultures exposed to diclofenac soon become depressed and die with signs of severe visceral gout and renal damage on necropsy. The molecular mechanism behind toxicity and renal excretion of uric acid is still poorly understood. With the clinical pictures suggesting renal uric acid excretion as the target site for toxicity, as a first step the following study was undertaken to determine the uric acid excretory pathways present in the African white-backed vulture (Gyps africanus) (AWB), one of the species susceptible to toxicity. Using transcriptome analysis, immunohistochemistry and functional predictions, we demonstrated that AWB makes use of the organic anion transporter 2 (OAT2) for their uric acid excretion. RT-qPCR analysis subsequently demonstrated relatively similar expression of the OAT2 transporter in the vulture and chicken. Lastly docking analysis, predicted that the non-steroidal drugs induce their toxicity through an allosteric binding.
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spelling pubmed-80960822021-05-17 Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney Nethathe, Bono Phaswane, Rephima Abera, Aron Naidoo, Vinny PLoS One Research Article Gyps species have been previously shown to be highly sensitive to the toxic effects of diclofenac, when present in their food sources as drug residues following use as a veterinary medicine. Vultures exposed to diclofenac soon become depressed and die with signs of severe visceral gout and renal damage on necropsy. The molecular mechanism behind toxicity and renal excretion of uric acid is still poorly understood. With the clinical pictures suggesting renal uric acid excretion as the target site for toxicity, as a first step the following study was undertaken to determine the uric acid excretory pathways present in the African white-backed vulture (Gyps africanus) (AWB), one of the species susceptible to toxicity. Using transcriptome analysis, immunohistochemistry and functional predictions, we demonstrated that AWB makes use of the organic anion transporter 2 (OAT2) for their uric acid excretion. RT-qPCR analysis subsequently demonstrated relatively similar expression of the OAT2 transporter in the vulture and chicken. Lastly docking analysis, predicted that the non-steroidal drugs induce their toxicity through an allosteric binding. Public Library of Science 2021-05-04 /pmc/articles/PMC8096082/ /pubmed/33945567 http://dx.doi.org/10.1371/journal.pone.0250408 Text en © 2021 Nethathe et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nethathe, Bono
Phaswane, Rephima
Abera, Aron
Naidoo, Vinny
Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
title Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
title_full Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
title_fullStr Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
title_full_unstemmed Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
title_short Molecular characterization of Gyps africanus (African white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
title_sort molecular characterization of gyps africanus (african white-backed vulture) organic anion transporter 1 and 2 expressed in the kidney
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096082/
https://www.ncbi.nlm.nih.gov/pubmed/33945567
http://dx.doi.org/10.1371/journal.pone.0250408
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