Abstract
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.
Funder
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular - CNPq
Fundação de Amparo à Pesquisa do Estado de São Paulo
Núcleo de Pesquisa em Moléculas Bioativas de Artrópodes Vetores
Publisher
Public Library of Science (PLoS)
Cited by
7 articles.
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