1350 Int. J. Morphol., 36(4):1350-1355, 2018. Vitamin E Protects Against Hepatocyte Ultrastructural Damage Induced by High Fat Diet in a Rat Model of Pre-Diabetes La Vitamina E Protege contra el Daño Ultraestructural de los Hepatocitos Inducido por la Dieta Alta en Grasas en un Modelo de Pre-diabetes en Ratas Mohamed Abd Ellatif 1,5 ; Abbas O El Karib 2 ; Mohammad Dallak 2 ; Refaat A Eid 3 ; Rihab Al-Ani 4 & Mohamed A Haidara 2,6 ELLATIF, M. A.; EL KARIB, A. O; DALLAK, M.; EID, R. A.; AL-ANI, R. & HAIDARA, M. A. Vitamin E protects against hepatocyte ultrastructural damageinduced by high fat diet in a rat model of pre-diabetes. Int. J. Morphol., 36(4):1350-1355, 2018. SUMMARY: We sought to investigate the potential protective effect of Vitamin E supplementation against hepatocyte ultrastructural alterations induced by high fat diet (HFD) in a rat model of pre-diabetes. Therefore, rats were either fed with HFD (model group) or a standard laboratory chow (control group) for 12 weeks before being sacrificed. The protective group fed on a HFD and started the treatment with vitamin E (100 mg/kg/day, i.p) from day 1 until being sacrificed at week 12. The harvested liver tissues were examined using transmission electron microscopy (TEM) and blood samples were assayed for biomarkers of liver injury and pre- diabetes. TEM images showed that HFD induced profound pathological changes to the hepatocyte ultrastructure as demonstrated by degenerated hepatocytes with damaged cytoplasm that have mitochondrial swelling, dilation of endoplasmic reticulum, blebbing of plasma membranes, and cytoplasmic accumulations of lipid droplets and vacuoles, which were substantially but not completely protected with vitamin E. In addition, HFD significantly (p<0.05) augmented biomarkers of liver injury and pre-diabetes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C), which were significantly (p<0.05) reduced with vitamin E except TNF-α and TC. Furthermore, none of these biomarkers were reduced to the control level by vitamin E. We conclude that vitamin E is a partial protective agent against HFD-induced liver injury and pre-diabetes. KEY WORDS: Hepatocyte ultrastructure; Pre-diabetes; Hepatic steatosis; Vitamin E; Animal model. INTRODUCTION The rapid rise in obesity, particularly among children in industrial and wealthy countries is a major public health problem and it is estimated that there are 35 million obesity- related deaths worldwide per year (Lustig et al., 2012). Ab- dominal obesity is a criteria of the metabolic syndrome, also called pre-diabetes, which is a cluster of abnormalities characterized by insulin resistance, inflammation, oxidative stress, hypertension and dyslipidaemia which carries increased risk of type 2 diabetes mellitus(T2DM), cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and cancer (Kopelman, 2000; Eckel et al., 2005; Grattagliano et al., 2008). NAFLD is the hepatic component of pre-diabetes (Paschos & Paletas, 2009) that affects liver function due to fat accumulation (hepatic steatosis) caused by dysfunction of fat metabolism in the liver (Benlhabib et al., 2004), which can lead to, if not treated, more serious complications such as nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, liver failure and even hepatocellular car- cinoma (Choi & Diehl, 2005; Paschos & Paletas). NAFLD is becoming the most common cause of liver disease in Western countries (de Alwis & Day, 2008), and is associated with significant liver related morbidity and mortality (Byrne & Targher, 2015). The precise mechanisms of NAFLD are still not fully understood and there is no specific medicine to cure the 1 Department of Clinical Biochemistry College of Medicine, King Khalid University, Saudi Arabia. 2 Department of Physiology College of Medicine, King Khalid University, Saudi Arabia. 3 Department of Pathology College of Medicine, King Khalid University, Saudi Arabia. 4 Department of Microbiology College of Medicine, King Khalid University, Saudi Arabia. 5 Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 6 Department of Physiology, Kasr al-Aini Faculty of Medicine, Cairo University, Cairo, Egypt. This work was supported by King Khalid University grant number KKU-Project No. R.G.P.1/27/38.