ORY supplementation mitigates acetaminophen-induced acute liver failure in male mice: role of oxidative stress and apopt
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ORIGINAL ARTICLE
ORY supplementation mitigates acetaminophen-induced acute liver failure in male mice: role of oxidative stress and apoptotic markers Marcelo Gomes de Gomes 1 & Lucian Del Fabbro 1,2 & André Rossito Goes 1 & Leandro Cattelan Souza 1 & Silvana Peterini Boeira 1 & Cristiano Ricardo Jesse 1 Received: 29 March 2020 / Accepted: 23 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The aim of the present study was to assess the possible protective effect of γ-oryzanol (ORY) supplementation in a model of acute liver failure (ALF) induced by acetaminophen (APAP) in mice. Male Swiss strain mice were supplemented with ORY (10 and 50 mg/kg, per oral route) daily for 7 days. One hour after the last supplementation, animals received APAP (300 mg/kg, intraperitoneal). Twenty-four hours after APAP administration, mice were euthanized, and biochemical and histopathological determinations were performed. Histopathological analysis revealed that APAP caused vascular congestion, loss of cellular structure, and cellular infiltration in hepatocytes. Moreover, it caused oxidative damage (enzymatic and non-enzymatic analysis of oxidative stress), with loss of hepatic function leading to cell apoptosis (apoptotic parameters). ORY supplementation (ORY10 and ORY-50) protected against all changes in ALF model. Thus, the protective effect of ORY supplementation was due to modulation of antioxidant defenses avoiding the apoptotic process. Keywords Anti-apoptotic . Antioxidant . Hepatoprotective . Caspase . Nutraceutical
Introduction The liver is essential for the human organism, because it is involved in several metabolic processes such as detoxification of drugs and xenobiotic compounds. Liver injury originated by occasional exposure (alcohol ingestion, viral infections), chemical exposure (drugs), or accidental exposure (hepatotoxins) (Chen et al. 2020) has become a public health problem, because it can lead to chronic hepatitis. Acetaminophen (APAP; N-acetyl-p-aminophenol) is a drug with analgesic and antipyretic action widely used worldwide. APAP is an easily accessible drug for population, being the
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01930-1) contains supplementary material, which is available to authorized users. * Marcelo Gomes de Gomes [email protected] 1
Laboratory of Pharmacological and Toxicological evaluations applied to Bioactive Molecules (Laftambio Pampa), Federal University of Pampa, Campus Itaqui, Itaqui, RS 97650-000, Brazil
2
Department of Pharmacy, University of Contested, Campus Mafra, Mafra 89306-076, Brazil
cases of overdose this medication, the main cause of acute liver failure (ALF) in several countries (Larsen and Wendon 2014). The metabolism of APAP occurs through cytochrome P450 enzymes that result in excessive formation of N-acetylq-benzoquinone imine (NAPQI). The NAPQI metabolite causes glutathione depletion (GSH), triggers oxidative stress (OS), and increased of inflammatory pro
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