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Effects of Artepillin C in acute liver toxicity induced by acetaminophen

Grant number: 11/12749-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Helio Vannucchi
Grantee:João Felipe Rito Cardoso
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Analgesics are the main cause accidents from toxic agents exposure. Acetaminophen (APAP, 4-hidroxiacetanilida) presents analgesic and antipyretic properties, despite being safe in therapeutic doses, in cases of overdose promotes hepatic necrosis in humans and animals. The APAP is bioactivated by cytochrome P450 in a highly reactive toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) that is detoxified by conjugation of glutathione (GSH), however, the formation of excessive NAPQI binds to cellular and mitochondrial proteins, altering membrane permeability of mitochondria, increased oxidative stress and inducing hepatic necrosis. In the search for new drugs and therapeutic interventions, researchers have been studying plant extracts and natural products, looking for anti-oxidants substances, flavonoids presents antioxidant, antiviral, anti-inflammatory actions. The plant Baccharis dracunculifolia DC (Asteraceae), popularly known as "Alecrim do Campo", native from southeastern Brazil is rich in many substances, including the flavonoids Artepillin C with differents properties including antimicrobial, anti-tumor, inducer of apoptosis, immunomodulatory, antioxidant, anti-inflammatory and analgesic and suppressing lipid peroxidation of membranes and the formation of 8-hydroxy-deoxyguanosine.