title: Is anorexia in thioacetamide-induced cirrhosis related to an altered brain serotonin concentration?
abstract: Anorexia or loss of appetite, one of the most typical symptoms observed in experimental and human cirrhosis, has been proposed to be associated with altered brain serotonin (5-HT) metabolism. In order to evaluate this hypothesis, brain 5-HT, its precursor tryptophan (TRP) and its metabolite 5-hydroxyindole-acetic acid (5-HIAA) were measured in brains of rats with thioacetamide (TAA)-induced liver cirrhosis. Thioacetamide at a dose of 500 mg/l in drinking water was administered for 6 weeks and during this period food intake was carefully measured in order to monitor the loss of appetite or decrease in food intake observed in cirrhosis. Concentrations of brain TRP, 5-HT and 5-HIAA were measured by HPLC with electrochemical detection. In TAA-treated rats, concentrations of 5-HT, TRP and 5-HIAA were increased in brain (44%, 33% and 36% of controls, p < 0.01). In plasma and liver of cirrhotic rats, TRP levels were increased (195% and 43%; p < 0.01). Plasma glucose and albumin levels were decreased (50%; p < 0.01 and 31%). Food intake, growth rate and locomotor activity of TAA-treated rats also decreased (73%, 22% and 73% of controls; p < 0.01). The results of this study show that brain 5-HT concentration in rats is increased in TAA-treated rats and it may, therefore, play an important role in the pathogenesis of anorexia associated with TAA-induced cirrhosis.
authors.affiliation: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Unit, University of Karachi, Pakistan. saidah13@yahoo.com
authors.forename: Saida
authors.initials: S
authors.lastname: Haider
authors.forename: Sadia
authors.initials: S
authors.lastname: Saleem
authors.forename: Saima
authors.initials: S
authors.lastname: Shameem
authors.forename: Shahida P
authors.initials: SP
authors.lastname: Ahmed
authors.forename: Tahira
authors.initials: T
authors.lastname: Parveen
authors.forename: Darakhshan J
authors.initials: DJ
authors.lastname: Haleem
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000150:complications*; D001522:Behavior, Animal; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004195:Disease Models, Animal; D004326:Drinking; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005355:Fibrosis / Q000139:chemically induced* / Q000150:complications*; D006897:Hydroxyindoleacetic Acid / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects; D010154:Pakistan; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000737:chemistry* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects; D013853:Thioacetamide / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D014364:Tryptophan / Q000097:blood
chemical_list: D001786:Blood Glucose; D012709:Serum Albumin; D013853:Thioacetamide; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan