title: Dietary supplementation with monounsaturated and long-chain polyunsaturated fatty acids influences the liver structural recovery and hepatocyte binuclearity in female Wistar rats in experimental cirrhosis induced by thioacetamide.
abstract: Oral administration of 300 mg/l thioacetamide (TAA) for 4 months causes hepatic lesions comparable to those described in alcoholic liver cirrhosis in humans and associated protein-energy malnutrition. In this sense, direct supplementation with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids (PUFAs) might provide an advantage in the correction of the fatty acid deficiency in these patients. PUFAs are essential components of cell membranes maintaining its fluidity and function, important energy sources, and precursors of eicosanoids. Moreover, these fatty acids also modulate gene transcription, mRNA stability, and cellular differentiation.
  
  
  METHODS
  Fifty-four female Wistar rats (Interfauna Ibérica, Barcelona, Spain) weighing 110-120 g were used in this study. The animals were divided into two groups: one group was treated with 300 mg/l TAA dissolved in drinking water during 4 months, and the other group, which served as a control, was given water without TAA. To evaluate the changes induced by the administration of TAA for 4 months, TAA-treated (n = 7) and control animals (n = 5) were killed. Then, the TAA treatment was stopped and the rest of the animals in both TAA and control groups were divided into three experimental groups and three control groups which received for 2 weeks different type of diets. Using the TAA-induced liver cirrhosis model in rats, we analysed the effects of dietary supplementation with MUFAs and PUFAs on binuclearity and ultrastructure of hepatocytes. After TAA-induced cirrhosis, we analysed whether dietary supplementation with fatty acids may restore the normal percentage of binucleated cells, as well as the ultrastructure, nuclear area, and nuclear/cytoplasm index of hepatocytes.
  
  
  RESULTS
  Treatment with TAA causes cirrhosis characterized by the appearance of parenchyma nodules and fibrous septae, as well as qualitative and quantitative alterations in liver and plasma lipids. Our results indicate that dietary MUFAs support hepatocyte recovery regarding its ultrastructural and morphometric values. However, PUFAs-enriched diets (n-3 and n-3 + n-6) do not correct hepatomegaly, fibrosis or lipid accumulation. Thus, dietary PUFAs do not enhance hepatocyte recovery from morphological and ultrastructural alterations.
  
  
  CONCLUSIONS
  In our experimental model of cirrhosis, dietary supplementation with a high proportion of long-chain PUFAs (n-3 or n-6) negatively influences liver recovery. This negative effect was likely due to the increased susceptibility of cell membranes to lipid peroxidation, together with an alteration in lipid metabolism.
authors.affiliation: Department of Cell Biology and Pathology Anatomy, University of Barcelona, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Fernández
authors.forename: L
authors.initials: L
authors.lastname: Fontana
authors.forename: A
authors.initials: A
authors.lastname: Gil
authors.forename: A
authors.initials: A
authors.lastname: Ríosc
authors.forename: M I
authors.initials: MI
authors.lastname: Torres
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D004042:Dietary Fats, Unsaturated / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008099:Liver; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide
chemical_list: D004042:Dietary Fats, Unsaturated; D005229:Fatty Acids, Monounsaturated; D013853:Thioacetamide