Research Article Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice Nancy Sayuri Uchida, 1 Saulo Euclides Silva-Filho, 1 Gabriel Fernando Esteves Cardia, 1 Edivaldo Cremer, 1 Francielli Maria de Souza Silva-Comar, 1 Expedito Leite Silva, 2 Ciomar Aparecida Bersani-Amado, 1 and Roberto Kenji Nakamura Cuman 1 1 Department of Pharmacology and Terapeutics, State University of Maring´ a, Avenida Colombo 5790, 870020-900 Maring´ a, PR, Brazil 2 Department of Chemistry, State University of Maring´ a, 87020-900 Maring´ a, PR, Brazil Correspondence should be addressed to Nancy Sayuri Uchida; n.sayuri@hotmail.com and Roberto Kenji Nakamura Cuman; rkncuman@uem.br Received 9 March 2017; Revised 27 April 2017; Accepted 25 May 2017; Published 22 June 2017 Academic Editor: Yuri Clement Copyright © 2017 Nancy Sayuri Uchida et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the efects of citral in a murine model of hepatotoxicity induced by APAP. Te liver function markers alanine aminotransferase (AL T), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GT) were determined to evaluate the hepatoprotective efects of citral. Te livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. Te efect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased signifcantly the levels of ALT, AST, ALP, and GT, MPO activity, and NO production. Te histopathological analysis showed an improvement of hepatic lesions in mice afer citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP. 1. Introduction Drug-induced liver injury is a signifcant clinical problem worldwide [1]. Most drug-induced liver injury and acute liver failure occur due to either accidental or intentional overdose of acetaminophen (N-acetyl-p-aminophenol, paracetamol, APAP) [2]. APAP is an antipyretic and analgesic drug used widely in clinics. When used at therapeutic doses, APAP is metabolized by glucuronidation or sulfation by the cytochrome p450 system into the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). Under normal circumstances, NAPQI is rapidly converted to nontoxic metabolites by glutathione (GSH). However, at large doses of APAP, NAPQI levels increase and may react with hepatic proteins, resulting in liver injury [3, 4]. Because of its dose-dependent toxicity, APAP-induced hepatic damage can be studied in animal models and most mechanisms are translatable to humans [2]. APAP-induced hepatotoxicity has been a signifcant issue for several years and diferent strategies have been studied, including the use of natural compounds with hepatoprotec- tive efects [5, 6]. Natural products are attracting the interest of many researchers to investigate their potential as drugs for the treatment of various diseases. Furthermore, there are many bioactive substances that are synthesized from constituents of essential oils (mixture of volatile and natural substances) that have some pharmacological activities [7]. In this con- text, monoterpene citral, an isomeric mixture of neral and geranial, a component of lemongrass oil, has been reported to have many biological activities such as antibacterial and anti-infammatory activities [8–10]. However, the protective efect of citral on APAP-toxicity remains unclear. Tus, the aim of the present study was to evaluate the efect of citral in hepatotoxicity induced by APAP. Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2017, Article ID 1796209, 9 pages https://doi.org/10.1155/2017/1796209