BACKGROUND: Hyperammonaemia is a serious metabolic disorder commonly observed in patients with hepatic failure. However, it is unknown whether hyperammonaemia has a direct adverse effect on the hepatocytes and thereby serves as both a cause and effect of hepatic failure. AIMS: The purposes were to determine whether hepatic injury can be caused by hyperammonaemia, and if so, screen the key genes involved in hyperammonaemia. METHODS: Hyperammonaemic rats were established via intragastric administration of the ammonium chloride solution. The liver tissues were assessed via biochemistry, histology, immunohistochemistry and microarray analysis. Selected genes were confirmed by quantitative RT-PCR. RESULTS: Administration of the ammonium chloride caused the hyperammonaemia, accompanied with the changes of plasma markers indicating hepatic injury. A pathological assessment demonstrated increased apoptosis and higher level of cyclin D1 and cyclin A in hyperammonaemic rat liver. Microarray was performed on the liver samples and 198 differentially expressed genes were identified in hyperammonaemic rats and validated by quantitative RT-PCR. These genes were associated with many vital functional classes and belonged to different signal transduction pathways. CONCLUSIONS: This study demonstrates that hyperammonaemia can directly induce hepatic injury via the hepatocyte apoptosis. Gene expression profile may provide the possible explanations and mechanisms for the hepatic injury induced by hyperammonaemia.
BACKGROUND: Hyperammonaemia is a serious metabolic disorder commonly observed in patients with hepatic failure. However, it is unknown whether hyperammonaemia has a direct adverse effect on the hepatocytes and thereby serves as both a cause and effect of hepatic failure. AIMS: The purposes were to determine whether hepatic injury can be caused by hyperammonaemia, and if so, screen the key genes involved in hyperammonaemia. METHODS: Hyperammonaemic rats were established via intragastric administration of the ammonium chloride solution. The liver tissues were assessed via biochemistry, histology, immunohistochemistry and microarray analysis. Selected genes were confirmed by quantitative RT-PCR. RESULTS: Administration of the ammonium chloride caused the hyperammonaemia, accompanied with the changes of plasma markers indicating hepatic injury. A pathological assessment demonstrated increased apoptosis and higher level of cyclin D1 and cyclin A in hyperammonaemic rat liver. Microarray was performed on the liver samples and 198 differentially expressed genes were identified in hyperammonaemic rats and validated by quantitative RT-PCR. These genes were associated with many vital functional classes and belonged to different signal transduction pathways. CONCLUSIONS: This study demonstrates that hyperammonaemia can directly induce hepatic injury via the hepatocyte apoptosis. Gene expression profile may provide the possible explanations and mechanisms for the hepatic injury induced by hyperammonaemia.
Authors: Cristina R Bosoi; Mariana M Oliveira; Rafael Ochoa-Sanchez; Mélanie Tremblay; Gabriella A Ten Have; Nicolaas E Deutz; Christopher F Rose; Chantal Bemeur Journal: Metab Brain Dis Date: 2016-12-15 Impact factor: 3.584
Authors: Rubén Rodríguez-Agudo; Naroa Goikoetxea-Usandizaga; Marina Serrano-Maciá; Pablo Fernández-Tussy; David Fernández-Ramos; Sofía Lachiondo-Ortega; Irene González-Recio; Clàudia Gil-Pitarch; María Mercado-Gómez; Laura Morán; Maider Bizkarguenaga; Fernando Lopitz-Otsoa; Petar Petrov; Miren Bravo; Sebastiaan Martijn Van Liempd; Juan Manuel Falcon-Perez; Amaia Zabala-Letona; Arkaitz Carracedo; Jose Vicente Castell; Ramiro Jover; Luis Alfonso Martínez-Cruz; Teresa Cardoso Delgado; Francisco Javier Cubero; María Isabel Lucena; Raúl Jesús Andrade; Jon Mabe; Jorge Simón; María Luz Martínez-Chantar Journal: Antioxidants (Basel) Date: 2022-04-30