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Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice

Acetaminophen (N-acetyl-p-aminophenol, APAP) overdose is the most common cause of drug-induced liver injury (DILI). Although the primary hepatic damage is induced by APAP-derived toxic intermediates resulting from cytochrome P450 metabolism, immune components also play an important role in DILI path...

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Autores principales: Assis, Josiane B., Cogliati, Bruno, Esteves, Eliane, Capurro, Margareth L., Fonseca, Denise M., Sá-Nunes, Anderson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869984/
https://www.ncbi.nlm.nih.gov/pubmed/33556084
http://dx.doi.org/10.1371/journal.pone.0245788
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author Assis, Josiane B.
Cogliati, Bruno
Esteves, Eliane
Capurro, Margareth L.
Fonseca, Denise M.
Sá-Nunes, Anderson
author_facet Assis, Josiane B.
Cogliati, Bruno
Esteves, Eliane
Capurro, Margareth L.
Fonseca, Denise M.
Sá-Nunes, Anderson
author_sort Assis, Josiane B.
collection PubMed
description Acetaminophen (N-acetyl-p-aminophenol, APAP) overdose is the most common cause of drug-induced liver injury (DILI). Although the primary hepatic damage is induced by APAP-derived toxic intermediates resulting from cytochrome P450 metabolism, immune components also play an important role in DILI pathophysiology. Aedes aegypti saliva is a source of bioactive molecules with in vitro anti-inflammatory and immunomodulatory activities. However, evidences on the therapeutic use of Ae. aegypti salivary preparations in animal models of relevant clinical conditions are still scarce. Thus, the present study was designed to evaluate the protective role of Ae. aegypti saliva in a murine model of APAP-induced DILI. C57BL/6 mice were exposed to Ae. aegypti bites 2 hours after APAP overdose. Biochemical and immunological parameters were evaluated in blood and liver samples at different time points after APAP administration. Exposure to Ae. aegypti saliva attenuated liver damage, as demonstrated by reduced hepatic necrosis and serum levels of alanine aminotransferase in APAP-overdosed mice. The levels of hepatic CYP2E1, the major enzyme responsible for the bioactivation of APAP, were not changed in Ae. aegypti exposed animals, suggesting no effects in the generation of hepatotoxic metabolites. On the other hand, mice treated with Ae. aegypti saliva following APAP overdose presented lower serum concentration of TNF-α, IL-6, IL-1β and IL-10, as well as reduced frequency of inflammatory cell populations in the liver, such as NKT cells, macrophages and dendritic cells. These findings show that Ae. aegypti saliva has bioactive molecules with therapeutic properties and may represent a prospective source of new compounds in the management of DILI-associated inflammatory disorders and, perhaps, many other inflammatory/autoimmune diseases.
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spelling pubmed-78699842021-02-11 Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice Assis, Josiane B. Cogliati, Bruno Esteves, Eliane Capurro, Margareth L. Fonseca, Denise M. Sá-Nunes, Anderson PLoS One Research Article Acetaminophen (N-acetyl-p-aminophenol, APAP) overdose is the most common cause of drug-induced liver injury (DILI). Although the primary hepatic damage is induced by APAP-derived toxic intermediates resulting from cytochrome P450 metabolism, immune components also play an important role in DILI pathophysiology. Aedes aegypti saliva is a source of bioactive molecules with in vitro anti-inflammatory and immunomodulatory activities. However, evidences on the therapeutic use of Ae. aegypti salivary preparations in animal models of relevant clinical conditions are still scarce. Thus, the present study was designed to evaluate the protective role of Ae. aegypti saliva in a murine model of APAP-induced DILI. C57BL/6 mice were exposed to Ae. aegypti bites 2 hours after APAP overdose. Biochemical and immunological parameters were evaluated in blood and liver samples at different time points after APAP administration. Exposure to Ae. aegypti saliva attenuated liver damage, as demonstrated by reduced hepatic necrosis and serum levels of alanine aminotransferase in APAP-overdosed mice. The levels of hepatic CYP2E1, the major enzyme responsible for the bioactivation of APAP, were not changed in Ae. aegypti exposed animals, suggesting no effects in the generation of hepatotoxic metabolites. On the other hand, mice treated with Ae. aegypti saliva following APAP overdose presented lower serum concentration of TNF-α, IL-6, IL-1β and IL-10, as well as reduced frequency of inflammatory cell populations in the liver, such as NKT cells, macrophages and dendritic cells. These findings show that Ae. aegypti saliva has bioactive molecules with therapeutic properties and may represent a prospective source of new compounds in the management of DILI-associated inflammatory disorders and, perhaps, many other inflammatory/autoimmune diseases. Public Library of Science 2021-02-08 /pmc/articles/PMC7869984/ /pubmed/33556084 http://dx.doi.org/10.1371/journal.pone.0245788 Text en © 2021 Assis et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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
Assis, Josiane B.
Cogliati, Bruno
Esteves, Eliane
Capurro, Margareth L.
Fonseca, Denise M.
Sá-Nunes, Anderson
Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
title Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
title_full Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
title_fullStr Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
title_full_unstemmed Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
title_short Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
title_sort aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869984/
https://www.ncbi.nlm.nih.gov/pubmed/33556084
http://dx.doi.org/10.1371/journal.pone.0245788
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