Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats Bahar Bilgin Sokmen a,1 , Sevim Tunali b,⇑ , Refiye Yanardag b,2 a Department of Chemistry, Faculty of Arts and Sciences, Giresun University, 28049 Giresun, Turkey b Department of Chemistry, Faculty of Engineering, Istanbul University, 34320 Avcilar, Istanbul, Turkey article info Article history: Received 26 April 2012 Accepted 28 July 2012 Available online 4 August 2012 Keywords: Vitamin U Valproic acid Liver enzymes Rat Hepatotoxicity abstract In this study, we aimed to investigate the effects of vitamin U (Vit U) on valproic acid (VPA)-induced liver damage. Female Sprague Dawley rats were randomly divided into four groups. Group I was intact control animals. Group II was control rats given Vit U (50 mg/kg/day) for fifteen days. Group III was given only VPA (500 mg/kg/day) for fifteen days. Group IV was given VPA + Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals were fasted overnight and then sacrificed under ether anesthesia. Liver tissue was taken from animals, homogenized in 0.9% saline to make up to 10% homogenate. Liver aspartate and alanine trans- aminases, alkaline phosphatase, lactate dehydrogenase, myeloperoxidase, sorbitol dehydrogenase, gluta- mate dehydrogenase and xanthine oxidase activities and lipid peroxidation levels were increased and paraoxonase activity and glutathione levels were decreased in VPA group. Treatment with Vit U reversed these effects. These results demonstrated that administration of Vit U is a potentially beneficial agent to reduce the liver damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indi- cations and consist of a group of drugs that are highly susceptible to interactions. During the last years several new AEDs have been marketed. Initially, all of new AEDs are licensed for add-on therapy for epilepsy patients. Several AEDs as lamotrigine, valproic acid, oxycarbamazepine, pregabalin, gabapentin, and topiramate are also increasingly used in other indications as psychiatry, neuro- pathic pain and migraine (Johannessen Landmark, 2008; Johannes- sen Landmark et al., 2009). Valproic acid (2-propyl-pentanoic acid, VPA) is recommended for several therapeutic purposes. For many years, it has been used in treatment of epilepsy and considered to be a safe antiepileptic drug in a wide range of epileptic conditions in children and adults (Garcia-Morales et al., 2007). Additionally VPA has been shown to be effective in the prevention of migraine headaches (Shelton and Connelly, 1996). The therapeutic applications of VPA may have the potential to be extended to the management of certain types of cancer (Minnuci and Pelicci, 2006) and human immunodeficiency virus infection (Lehrman et al., 2005; Minnuci and Pelicci, 2006). VPA is usually well tolerated, but serious complications including hepatotoxicity, hyperammonemic encephalopathy, fatal hemor- rhagic pancreatitis, teratogenicity, bone marrow suppresion may occur (Perruca, 2002; Lheureux and Hantson, 2009). Certain vegetables, in particular cabbage contain a nutritional factor with reported antiulcer properties (Roche-Vitec, 1990). This factor, S-methyl methionine sulphonium chloride, has also been called vitamin U (Vit U) (from the latin ulcus meaning a sore or ul- cer) (Kopinski et al., 2007) although its classification as a vitamin has not yet been accepted (Roche-Vitec, 1990). Vit U is present in the largest quantity in species belonging to the Brassicaceae family (Rácz et al., 2008). Vit U deficiency is thought to be a possible cause of gastric ulcers (Watanabe et al., 1996). Antiulcer properties, anti- inflammatory action, reduction of blood lipid, antidepressant ac- tion, wound-healing, adipocyte differentiation and cytoprotective effects of Vit U have been demonstrated (Urazaeva, 1976; Stoliarov and Mys’ko, 1981; Salim, 1992; Kim et al., 2010; Lee et al., 2012). In this study, we aimed to investigate the effects of Vit U on VPA-induced liver damage. 0278-6915/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fct.2012.07.056 Abbreviations: Vit U, vitamin U; VPA, valproic acid; AEDs, antiepileptic drugs; GSH, reduced glutathione; LPO, lipid peroxidation; AST, aspartate transaminase; ALT, alanine transaminase; ALP, alkaline phosphatase; LDH, lactate dehydrogenase; MPO, myeloperoxidase; SDH, sorbitol dehydrogenase; GLDH, glutamate dehydro- genase; XO, xanthine oxidase; PON, paraoxonase; NO, nitric oxide; ROS, reactive oxygen species; NADH, nicotinamide adenine dinucleotide reduced. ⇑ Corresponding author. Tel.: +90 212 4737070/17791; fax: +90 212 4737180. E-mail addresses: baharsokmen@yahoo.com (B.B. Sokmen), sevtunali@gmail. com (S. Tunali), refiyeyanardag@yahoo.com (R. Yanardag). 1 Tel.: +90 4543101488/1466; fax: +90 4543101477. 2 Tel.: +90 212 4737037; fax: +90 212 4737180. Food and Chemical Toxicology 50 (2012) 3562–3566 Contents lists available at SciVerse ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox