Òdena G, Miquel M, Serafín A, Galan A, Morillas R, Planas R, Bartolí R. Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats. World J Gastroenterol 2012; 18(17): 2084-2091 [PMID: 22563196 DOI: 10.3748/wjg.v18.i17.2084]
Corresponding Author of This Article
Ramon Bartolí, PhD, Hepatology Unit, Department of Gastroenterology, Germans Trias i Pujol Health Sciences Research Institute, 08916 Badalona, Spain. rbartolisole@gmail.com
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World J Gastroenterol. May 7, 2012; 18(17): 2084-2091 Published online May 7, 2012. doi: 10.3748/wjg.v18.i17.2084
Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats
Gemma Òdena, Mireia Miquel, Anna Serafín, Amparo Galan, Rosa Morillas, Ramon Planas, Ramon Bartolí
Gemma Òdena, Ramon Planas, Ramon Bartolí, Hepatology Unit, Department of Gastroenterology, Germans Trias i Pujol Health Science Research Institute, 08916 Badalona, Spain
Gemma Òdena, Mireia Miquel, Rosa Morillas, Ramon Planas, Ramon Bartolí, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
Mireia Miquel, Department of Gastroenterology, Corporació Sanitària Parc Taulí, 08208 Sabadell, Spain
Anna Serafín, Platform of Laboratory Animal Applied Research, Parc Científic de Barcelona, 08028 Barcelona, Spain
Amparo Galan, Department of Biochemistry, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
Rosa Morillas, Ramon Planas, Liver Unit, Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
Author contributions: Òdena G and Miquel M contributed equally to this work; Miquel M, Morillas R, Planas R and Bartolí R designed the research; Òdena G, Miquel M and Bartolí R performed the experimental procedures; Serafín A performed the histological analysis; Galan A performed the biochemical analysis; Òdena G, Morillas R, Planas R and Bartolí R analyzed the data; Òdena G, Miquel M and Bartolí R wrote the paper.
Supported by A grant from the Instituto de Salud Carlos III, PI051371, PI080809
Correspondence to: Ramon Bartolí, PhD, Hepatology Unit, Department of Gastroenterology, Germans Trias i Pujol Health Sciences Research Institute, 08916 Badalona, Spain. rbartolisole@gmail.com
Telephone: +34-93-4978688 Fax: +34-93-4978654
Received: May 17, 2011 Revised: June 25, 2011 Accepted: August 15, 2011 Published online: May 7, 2012
Abstract
AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.
METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed.
RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis.
CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy.
