Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats Sema Gedik a , Mehmet Erman Erdemli b , Mehmet Gul c , Birgul Yigitcan c , Harika Gozukara Bag d , Zeynep Aksungur e , Eyup Altinoz f, ⁎ a Department of Chemistry, Faculty of Sciences, Karabuk University, Karabuk, Turkey b Department of Medical Biochemistry, Medical Faculty, Nigde Omer Halisdemir University, Nigde, Turkey c Department of Histology and Embryology, Medical Faculty, Inonu University, Malatya, Turkey d Department of Biostatistics, Medical Faculty, Inonu University, Malatya, Turkey e Department of Medical Biochemistry, Medical Faculty, Inonu University, Malatya, Turkey f Department of Medical Biochemistry, Medical Faculty, Karabuk University, Karabuk, Turkey ARTICLE INFO Keywords: Acrylamide Crocin Oxidative stress Hepatotoxicity ABSTRACT The objective of the present study is the treatment of oxidative damage caused by acrylamide induced oxidative stress in rats with the administration of a strong antioxidant, namely crocin. High acrylamide (AA) levels have genotoxic, carcinogenic and neurotoxic effects on living organisms. In the present study, 40 Wistar rats were randomly divided into four equal groups. These groups were control, acrylamide (25 mg/kg), crocin (50 mg/kg), acrylamide + crocin (25 mg/kg acrylamide and 50 mg/kg crocin) groups. At the end of the application, bio- chemical and histological variations were examined in liver and blood samples. It was observed that acrylamide administration significantly decreased liver GSH and TAS levels when compared to the control group. On the contrary, it was also observed that AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels increased as a result of acrylamide administration. Histopathological examinations demonstrated inflammatory cell in- filtration, hepatocellular necrosis and hemorrhage areas in AA group liver sections. Furthermore, in- tracytoplasmic vacuolization was detected in hepatocytes. After crocin treatment, it was observed that GSH and TAS levels increased while AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels decreased. Significant decreases were observed in inflammatory cell infiltration and vascular congestion in liver sections and intracytoplasmic vacuolization in hepatocytes after the crocin treatment, while no hepatocellular necrosis and hemorrhages were observed. In the present study, it was demonstrated that crocin treatment removed acrylamide induced liver damage due to the strong antioxidant properties of crocin. 1. Introduction Acrylamide (AA) is used as a chemical additive in industrial was- tewater treatment, textile industry, printing and production of cos- metics. The fact that AA was not produced in the nature and could only be chemically synthesized was not accepted until 2000. A group of researchers in Stockholm University found that high amounts of acry- lamide were formed in foods that were cooked under high temperatures in a study conducted between 2000 and 2002, and the study caused a sudden interest in acrylamide in scientific circles [1,2]. The World Health Organization (WHO), the United Nations Food and Agriculture Organization (FAO) [3] and the US Food and Drug Administration (FDA) stated that foodborne acrylamide could be a serious threat to human health after the Swedish scientists announced the formation of acrylamide in carbohydrate-rich food in 2002. AA might have carci- nogenic and neurotoxic effects due to various mechanisms, and thus, International Cancer Research Agency described AA as carcinogenic in humans [4]. AA intake is absorbed in the digestive system and trans- ferred to the liver at the rate of 4 mol of acrylamide in 1 mol of he- moglobin, which is then metabolized by two different pathways in the body and degraded. The first pathway is the conversion of AA to gly- cidamide, a genotoxic and mutagenic active substance, with cyto- chrome p450 (CYP)2E1 metabolism, a CYP-dependent isoenzyme, in the liver [5]. The CYP enzyme system is found in both liver and di- gestive tract mucosal epithelia [6]. AA, which is converted to glycida- mide by CYP2E1 in the liver, has a mutagenic effect and causes cancer in lungs, brain, kidneys, uterus and testis in several organisms including experimental animals [5]. CYP2E1 is the basic CYP isoenzyme and http://dx.doi.org/10.1016/j.biopha.2017.08.139 Received 24 July 2017; Received in revised form 30 August 2017; Accepted 30 August 2017 ⁎ Corresponding author. E-mail address: eyupaltinoz@karabuk.edu.tr (E. Altinoz). Biomedicine & Pharmacotherapy 95 (2017) 764–770 0753-3322/ © 2017 Elsevier Masson SAS. All rights reserved. MARK