Is anorexia in thioacetamide-induced cirrhosis related to an altered brain serotonin concentration?
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.
Haider
Saida
S
Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Unit, University of Karachi, Pakistan. saidah13@yahoo.com
Saleem
Sadia
S
Shameem
Saima
S
Ahmed
Shahida P
SP
Parveen
Tahira
T
Haleem
Darakhshan J
DJ
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
D001786:Blood Glucose; D012709:Serum Albumin; D013853:Thioacetamide; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan