Rat CCl4‐induced cirrhosis plus total portal vein ligation: a new model for the study of hyperammonaemia and brain oedema |
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Authors: | Mireia Miquel Ramon Bartolí Gemma Òdena Anna Serafín Eduard Cabré Amparo Galan Ignasi Barba Joan Córdoba Ramon Planas |
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Affiliation: | 1. Germans Trias i Pujol Health Science Research Institute, Badalona, Spain;2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain;3. Department of Gastroenterology, Corporació Sanitària Parc Taulí, Sabadell, Spain;4. *They share equal first authorship.;5. Liver Unit, Department of Gastroenterology, Hospital Germans Trias i Pujol, Badalona, Spain;6. Animal Research Department Universitat Autònoma de Barcelona, Barcelona, Spain;7. Department of Biochemistry, Hospital Germans Trias i Pujol, Badalona, Spain;8. Department of Cardiology. Hospital Universitari Vall d'Hebron, Barcelona, Spain;9. Liver Unit, Hospital Vall d'Hebrón, Barcelona, Spain |
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Abstract: | Introduction: Animal models used to study hyperammonaemic disorders related to chronic liver disease are unsatisfactory. These animals only develop hyperammonaemia and brain oedema when fed with diets supplemented with amonium acetate. Aim: To develop a novel experimental model of hyperammonaemia and brain oedema in CCl4‐induced cirrhosis in rats. Methods: Four groups were studied: rats with sham intervention (S), rats with total portal vein ligation (TPVL), cirrhotic rats (LC), and cirrhotic rats with TPVL (LC+TPVL). When ascites was diagnosed, oral glutamine challenge (OGC) test was performed. Blood, liver, lungs and brain samples were collected to quantify liver function parameters, plasmatic and cerebral ammonia, endotoxaemia, liver and brain histology, brain oedema and portosystemic shunting degree. Results: LC+TPVL rats showed a significant increase in portosystemic shunting when compared with LC group and a significant derangement in liver function when compared with TPVL group. These alterations resulted in a significant increase in plasmatic and brain ammonia concentrations and a higher plasmatic endotoxaemia as compared with others. Similarly, the area under OGC curve was significantly increased in LC+TPVL group as compared with the others, and correlates with portal shunting. Low‐grade brain oedema was only observed in LC+TPVL group. All cirrhotic groups showed liver regeneration nodules and type‐II Alzheimer astrocytes Conclusion: LC+TPVL reproduce the main alterations – portosystemic shunting, plasmatic and cerebral hyperammonaemia and low‐grade brain oedema – observed in cirrhotic patients with hepatic encephalopathy. |
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Keywords: | CCl4‐induced cirrhosis hepatic encephalopathy hyperammonaemia portal vein ligation rats |
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