Vol.:(0123456789) 1 3 Molecular and Cellular Biochemistry https://doi.org/10.1007/s11010-018-3311-2 Subchronic methionine load induces oxidative stress and provokes biochemical and histological changes in the rat liver tissue M. Stojanović 1  · D. Todorović 1  · Lj Šćepanović 1  · D. Mitrović 1  · S. Borozan 2  · V. Dragutinović 3  · M. Labudović‑Borović 4  · D. Krstić 3  · M. Čolović 5  · D. Djuric 1 Received: 31 October 2017 / Accepted: 27 January 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract The aim of this study was to assess the effects of L-cysteine (Cys) (7 mg/kg) and N-acetyl-L-cysteine (NAC) (50 mg/kg) in the rat liver caused by subchronic i.p. application of methionine (Met) (0.8 mmol/kg) during 21 days. Malondialdehyde (MDA) concentration, glutathione content (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and acetylcholinesterase (AchE) activities were determined in the liver tissue and activities of liver enzymes (AST, ALT, ALP, and GGT) and concentrations of total proteins and albumin were determinated in plasma/serum. Catalase, superoxide dis- mutase, and acetylcholinesterase activities were increased by Cys and NAC. Met caused periportal mononuclear infiltration and rare focal necrosis of hepatocytes. In Cys- and NAC-supplemented groups, intracellular edema and microvesicular fatty changes without necrosis were noticed. We observed decrease of AST, ALT, and ALP activity in the methionine-treated group. Our results indicate that Cys and NAC application can increase activity of antioxidative enzymes and prevent intensive histological changes in liver in condition of subchronic methionine exposure. Keywords Methionine · Antioxidants · Morphometry · Biochemical analysis · Liver · Rat Introduction Consumption of food with high methionine (Met) content like red meat, can be a risk factor for cardiovascular dys- functions, but the mechanisms still remain unclear. A diet rich in Met can damage the cardiovascular system through induction of oxidative stress, inflammation, and matrix remodeling [1]. Several reports demonstrated that Met-supplemented diet can induce hyperhomocysteinemia in mice and rats [2–4]. Relationship between hyperhomocysteinemia and cardiovas- cular diseases and its complications such as heart attacks and strokes have been described previously [5]. Recent stud- ies have recognized the correlation between elevated levels of homocysteine (Hcy) with impaired hepatic function, but pathways responsible for this influence of Hcy are still not completely understood. Hyperhomocysteinemia is recog- nized as one of the key indicators of impaired one-carbon metabolism [6]. Furthermore, Yu et al. demonstrated that Hcy can inhibit hepatocyte proliferation by inducing endo- plasmic reticulum stress [7]. Met is an essential sulfur-containing amino acid, which can be metabolized through two major pathways: remethyla- tion cycle and transsulfuration pathway. Met is converted to S-adenosyl methionine (SAM) which plays an important role in metabolism as methyl group donor in numerous of methyla- tion reactions of RNA, DNA, proteins, and lipids [8]. SAM is converted to S-adenosyl homocysteine (SAH) by donating methyl group to other molecules [9]. Hcy can enter transsul- furation pathway when cysteine (Cys) is produced by cysta- thionine γ-lyase [10]. A crucial role in the detoxification of * M. Stojanović mrj.stojanovic@gmail.com 1 Faculty of Medicine, Institute of Medical Physiology “Richard Burian”, University of Belgrade, Belgrade, Serbia 2 Department of Chemistry, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia 3 Faculty of Medicine, Institute of Medical Chemistry, University of Belgrade, Belgrade, Serbia 4 Faculty of Medicine, Institute of Histology and Embryology “Aleksandar Dj. Kostić”, University of Belgrade, Belgrade, Serbia 5 Department of Physical Chemistry, Institute of Nuclear Sciences “Vinča”, University of Belgrade, Belgrade, Serbia