Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice
Autor: | Josiane B Assis, Anderson Sá-Nunes, Denise Morais da Fonseca, Eliane Esteves, Margareth Lara Capurro, Bruno Cogliati |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Saliva Physiology Disease Vectors Pharmacology Mosquitoes White Blood Cells Mice Medical Conditions 0302 clinical medicine Animal Cells Aedes Immune Physiology Medicine and Health Sciences Medicine Immune Response Liver injury Innate Immune System Multidisciplinary biology digestive oral and skin physiology Eukaryota Alanine Transaminase Cytochrome P-450 CYP2E1 Animal Models CYP2E1 Natural killer T cell Body Fluids Insects Infectious Diseases Experimental Organism Systems Liver 030220 oncology & carcinogenesis Cytokines Anatomy Cellular Types Chemical and Drug Induced Liver Injury Research Article medicine.drug Arthropoda Immune Cells Science Immunology Antigen-Presenting Cells Mouse Models Aedes aegypti Aedes Aegypti Research and Analysis Methods 03 medical and health sciences Model Organisms Signs and Symptoms Immune system Animals Immunologic Factors Acetaminophen Inflammation Blood Cells business.industry Macrophages Organisms Biology and Life Sciences Insect Bites and Stings Cytochrome P450 Cell Biology Dendritic Cells Molecular Development biology.organism_classification medicine.disease Invertebrates ANTI-INFLAMATÓRIOS Insect Vectors Mice Inbred C57BL Species Interactions Disease Models Animal 030104 developmental biology Immune System Animal Studies biology.protein Clinical Medicine business Zoology Entomology Developmental Biology |
Zdroj: | PLoS ONE, Vol 16, Iss 2, p e0245788 (2021) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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 aegyptisaliva is a source of bioactive molecules within vitroanti-inflammatory and immunomodulatory activities. However, evidences on the therapeutic use ofAe.aegyptisalivary preparations in animal models of relevant clinical conditions are still scarce. Thus, the present study was designed to evaluate the protective role ofAe.aegyptisaliva in a murine model of APAP-induced DILI. C57BL/6 mice were exposed toAe.aegyptibites 2 hours after APAP overdose. Biochemical and immunological parameters were evaluated in blood and liver samples at different time points after APAP administration. Exposure toAe.aegyptisaliva 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 inAe.aegyptiexposed animals, suggesting no effects in the generation of hepatotoxic metabolites. On the other hand, mice treated withAe.aegyptisaliva 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 thatAe.aegyptisaliva 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. |
Databáze: | OpenAIRE |
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