[696] ROLE OF MELATONIN IN TREATMENT OF NONALCOHOLIC STEATOHEPATITIS IN RATS INDUCED BY HIGH FAT DIET

OK. ALCOHOLIC LIVER DISEASE, NAFLD AND DRUG-INDUCED LIVER DISEASE

16961 ROLE OF MELATONIN IN TREATMENT OF NONALCOHOLIC STEATOHEPATITIS IN RATS INDUCED BY HIGH FAT DIET N. Kuzu', 1.H. Bahcecioglu', K. Metin3, 1.H. Ozercan4, M. Tuzcu5, M. Yalniz', B. Ustundag7, K. Sahin8. 'Internal Medicine; 2Gustroenterologv; "Biochenzistry; 'Puthologv, Fuculw of Medicine, Firut Uniuersity, Eluzig; 'Biology, Fuculy of Science, Firut Uniuersih~, Eluzig; Gu,strorntrrolog~~; 7Biochemixtry, Fuculty of Medicine, Firut lJniuersity, Eluzig; 'Aninzul nutrition, Fuculw of Eterinuv, Firut lJniuersity, Eluzig, Turkey E-mail: [email protected] Aim: Melatonin is reported to exhibit a wide variety of biological effects, including antioxidant and anti-inflammatory. The aim of this study was to investigate to the therapeutic effect of administration of melatonin in the experimental nonalcoholic steatohepatitis model induced by high fat diet (HFD). Method: Forty male Sprague-Dawley rats were divided into four equal groups randomly. First group received only standard rat diet (control group). while groups 2, 3 and 4 were given HFD ad libitum. After the six weeks, 0.2 ml serum physiologic was injected intraperitoneally to the group 2, 1 Omgikgiday ve 50mgikglday melatonin was administered intraperitoneally to the group 3 and 4 (respectively) After eight weeks all rats were killed. Serum biochemistry, TNF-a, TGF fi, plasma and liver tissue malondialdehyde (MDA), glutathione levels were analyzed. Insulin resistance was assessed by Homa-R method. Histopathologically; steatosis, ballooning degeneration, inflammation and fibrosis were determined. Tmmunohistochemical staining was done for CYP2EI and a sMA expression. Results: Steatohepatitis was diagnosed all rats with fed high fat diet after eight weeks. Oxidative stres, CYP 2E1 expression, insulin resistance and serum TNF-a levels were increased in rats with steatohepatitis. Melatonin ( 1 0 or 50 mgikg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase. CYP 2E 1 expression, liver malondialdehyde level, insulin resistance and and serum TNF-a level were decreased by administration of melatonin. Glutathione levels were increased by administration of melatonin (10 mgikg, 50 mgikg). Balloning degeneration and a sMA expression were decreased only by administration of 50 mgikg dose of melatonin. Conclusion: This study shows that melatonin was effective in the treatment of experimental steatohepatitis by induced by high-fat diet possibly through its antioxidant actions and decreased insulin resistance. The administration of 50 mgikg dose of melatonin seems to more beneficial

16971 LIVER FIBROSIS IN HIV-INFECTED PATIENTS WITHOUT CHRONIC VIRAL HEPATITIS. PREVALENCE, CLINICAL CHARACTERISTICS AND POTENTIAL CAUSES P. Barreiro, L. Martin-Carbonero, 1. Maida, P. Labarga, C. Castellares, A. Ruiz-Sancho, F. Blanco, J. Gonzlez-Lahoz, V Soriano. Department of 1nfl.ctious Diseuses, Hospitul Curlos Ill, Mudrid, S p i n E-mail: [email protected] Background: Chronic liver disease in HTV+ patients is usually related to hepatotropic viral infections. The availability of non-invasive tools to assess liver fibrosis has allowed the identification of a group of HIV+ patients with advanced liver fibrosis (ALF) in the absence of recognisable etiology. Methods: HTV+ patients on follow-up at our institution were examined by FibroScan. ALF was defined as liver elasticity >9.5 Kpa, and cirrhosis as > I 4 Kpa. Only HTV+ patients with negative serum HCV-RNA and HBsAglHBV-DNA were included. Alcohol consumption was recorded by patient's interview; iron or copper overload, alpha- I -antitrypsin deficiency and auto-immune diseases were discarded. Exposure to antiretrovirals (ARV) was assessed at pharmacy database. Results: A total of 1,307 HIV+ patients without underlying viral liver disease were identified. Overall, 83% had no liver fibrosis, and 36 (2.7%)

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showed ALF. Halfofthe latest had cirrhosis, and 10 (0.8%) had developed hepatic decompensation. The distribution of risks groups was: TDUs 45%, MSM 35% and Heterosexuals 17%. In a univariate analysis, patients with and without ALF had older age (47 vs 44 years, p=0.006), elevated alcohol consumption (37 vs 15%, p=0.009), lower CD4 counts (481 vs 573 cellsiul, p=0.14), greater ALT (58 vs 39 IUiL, p=0.002), glucose (110 vs 102mg/dL, and similar cholesterol (204 p = 0.09), triglycerides (253 vs 185, p = 0.08), vs 208 mgidL, p = 0.23). A total of 1,601 patients-years of ARV exposure were examined in 233 randomly selected HTV+ patients. Only 5% were HAART-naive, while 54%, 45% and 74% had received NVP, EFV or PI. Mean duration of ARV exposure was 7.8 vs 6.6 years in ALF vs non-ALF (p=0.03). In a multivariate analysis (OR [95%CT], p), older age (1.71 [0.93-3.131, 0.08), alcohol abuse (3.15 [1.12-8.87, 0.03) and longer exposure to ritonavirboosted PI regimens (1.2 [0.97-1.531, 0.08) were associated with ALF. Conclusions: Advanced liver fibrosis in the absence of chronic hepatitis B/C may be recognisable in 2.7% of HIV+ patients. Although elevated alcohol consumption may contribute to liver disease in some cases, glucose and triglyceride elevations associated to prolonged administration of PI regimens may be another cause of liver damage in these patients.

16981 ALLELE AND GENOTYPE FREQUENCIES OF POLYMORPHIC CYP2E1, ADH2 AND ALDHZ IN A HUICHOL POPULATION B.E. Bastidas-Ramirez' , E. Zepeda-Carrillo', E. Gordillo-Bastidas' , D. Gordillo-Bastidas' , M. Gonzalez-Hita' , J.J. Garcia-Banuelos' , A. Panduro3. 'Moleculur Biology and Genomics, Center o f Health Sciences, liniuersiw of' Guudulujuru, Guudulujuru, Julisco; 'Autononzous Univer~xit?, of Nuyurit, Tepic, Nuyurit, Mexico.; 'Seruice of Moleculur Biology in Medicine of the Civil Hospitul Fruy Antonio Alculde, Guudulujuru, Julisco, Mexico E-mail: [email protected] Background and Aims: CYP2E1, ADH2 AND ALDH2 are the main ethanol metabolizing enzymes and also constitute candidate genes in alcoholism and alcoholic liver disease susceptibility. However, controversial results have been reported, maybe because a number of polymorphisms described are ethnic dependent. The aim of this study was to determine genotype and allele frequencies of Rsal, Maelll and Ksp6321 polymorphisms of CYP2E1, ADH2 and ALDH2, respectively in a huichol ethnic population from the west of Mkxico. Methods: We studied 106 huichol individuals living in an ethnic reservation from the western mountains of Mkxico and 331 subjects from the metropolitan area as control. Identification of the polymorphisms were carried out in peripheral leukocyte DNA by polymerase chain reaction amplification and ulterior restriction fragment length polymorphism (RFLP's) assay. We used RsaT, Mae111 and Ksp632T endonucleases for genotyping CYP2E1, ADH2 and ALDH2, respectively. Amplified and restriction fragments were visualized by agarose gel electrophoresis stained with ethidium bromide. Results: Genotype frequencies found in huichol population for CYP2E I polymorphism was as follows: l i l (wild type) 20%, heterocygous (1/2)54% and polymorphic (2/2) 26%. Frequencies in these genotypes 0.001) from those observed in control were significantly different (p i individuals: (1/1) 73%, (112) 23% and (2/2) 4%. Allelic frequencies for CYP2EI in huichol subjects were 47% wild type allele and 53% polymorphic allele; while 84.5% and 15.5%, respectively for the control (p < 001). For ADH2, we observed wild type polymorphism ( l i l ) in the 100% of the HUT. For ALDH2, 96% wild type and 4% heterocygous were found. Conclusion: Significant higher heterocygous genotype and polymorphic allele frequencies for CYP2El were found in huichol subjects in comparison with the urban population studied and other ethnic groups from