A morphological method for ammonia detection in liver.
Hyperammonemia is a metabolic condition characterized by elevated levels of ammonia and a common event in acute liver injury/failure and chronic liver disease. Even though hepatic ammonia levels are potential predictive factors of patient outcome, easy and inexpensive methods aiming at the detection of liver ammonia accumulation in the clinical setting remain unavailable. Thus, herein we have developed a morphological method, based on the utilization of Nessler´s reagent, to accurately and precisely detect the accumulation of ammonia in biological tissue. We have validated our method against a commercially available kit in mouse tissue samples and, by using this modified method, we have confirmed the hepatic accumulation of ammonia in clinical and animal models of acute and chronic advanced liver injury as well as in the progression of fatty liver disease. Overall, we propose a morphological method for ammonia detection in liver that correlates well with the degree of liver disease severity and therefore can be potentially used to predict patient outcome.
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Virginia
V
Gutiérrez-de-Juan
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Sergio
S
López de Davalillo
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
David
D
Fernández-Ramos
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Lucía
L
Barbier-Torres
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Imanol
I
Zubiete-Franco
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Pablo
P
Fernández-Tussy
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Jorge
J
Simon
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Fernando
F
Lopitz-Otsoa
Division of Pediatric Metabolism, University Hospital of Cruces, BioCruces Health Research Institute, University of the Basque Country, UPV/EHU, Barakaldo, Bizkaia, Spain.
Javier
J
de Las Heras
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Santander, Spain.|Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain.
Paula
P
Iruzubieta
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Santander, Spain.|Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain.
María Teresa
MT
Arias-Loste
Department of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy.
Erica
E
Villa
Division of Pediatric Metabolism, University Hospital of Cruces, BioCruces Health Research Institute, University of the Basque Country, UPV/EHU, Barakaldo, Bizkaia, Spain.|Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Santander, Spain.
Javier
J
Crespo
Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain.
Raúl
R
Andrade
Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain.
M Isabel
MI
Lucena
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Marta
M
Varela-Rey
Division of Digestive and Liver Disease, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Shelly C
SC
Lu
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
José M
JM
Mato
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
Teresa Cardoso
TC
Delgado
CIC bioGUNE (Center for Cooperative Research in Biosciences), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain.
María-Luz
http://orcid.org/0000-0002-6446-9911
ML
Martínez-Chantar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D002675:Child, Preschool; D003584:Cytological Techniques / Q000379:methods*; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017669:Mercury Compounds / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism; D055815:Young Adult
D007454:Iodides; D017669:Mercury Compounds; D000641:Ammonia; C009009:potassium tetraiodomercurate