title: Bumetanide increases manganese accumulation in the brain of rats with liver damage.
abstract: Hepatic encephalopathy is a common complication in cases of liver damage; it results from several factors, including the accumulation of toxic substances in the brain, e.g. manganese, ammonia and glutamine. We have previously reported that manganese favors ammonia and glutamine accumulation in the brain of cirrhotic rats, and we suggested that such effect could be mediated by manganese-elicited activation of the NKCC1 (Na(+)/K(+)/2Cl(-) cotransporter 1). To test this hypothesis, we used bumetanide, an NKCC1 blocker prescribed to treat ascites in cirrhotic patients; we expected that if NKCC1 was responsible for manganese-mediated ammonia buildup and the subsequent glutamine accumulation, bumetanide could counteract such effect and improve motor coordination. In addition, we considered essential to test the effect of bumetanide on manganese brain levels. We used a model of liver damage in rats, consisting in bile-duct ligation. Animals were exposed to manganese in the drinking water (1 mg/ml) for two weeks and ammonia in the food (20% w/w of ammonia acetate) during the second week after surgery. Bumetanide was administered intraperitoneally in the course of the ammonia treatment. We measured glutamine and manganese in three brain regions: frontal cortex, striatum and cerebellum. Bumetanide produced no effect on glutamine accumulation; however, because of bumetanide treatment, manganese was increased in the brain, and also the activity of gamma-glutamyl transferase in plasma; thus, we consider that the influence of bumetanide and similar diuretics on liver function and manganese homeostasis should be further studied.
authors: Neurochemistry Department, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez", Insurgentes sur 3877, La Fama, Tlalpan, Mexico 14269, D.F., Mexico. Electronic address: smontes@innn.edu.mx.
authors: Sergio
authors: S
authors: Montes
authors: Biological Systems Department, Autonomous Metropolitan University-Xochimilco, Calzada del Hueso 1100, Villa Quietud, Coyoacán, Mexico 04960, D.F., Mexico. Electronic address: armado_cruzazul@hotmail.com.
authors: Armando
authors: A
authors: Castro-Chávez
authors: Biological Systems Department, Autonomous Metropolitan University-Xochimilco, Calzada del Hueso 1100, Villa Quietud, Coyoacán, Mexico 04960, D.F., Mexico. Electronic address: circevi.floso@gmail.com.
authors: Circe
authors: C
authors: Florian-Soto
authors: Ethology, Wildlife and Laboratory Animals Department, Faculty of Veterinary Medicine and Zootechny, National Autonomous University of Mexico, University City, Coyoacán, Mexico 04360, D.F., Mexico. Electronic address: sarehy@gmail.com.
authors: Yessica
authors: Y
authors: Heras-Romero
authors: Neurochemistry Department, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez", Insurgentes sur 3877, La Fama, Tlalpan, Mexico 14269, D.F., Mexico. Electronic address: crios@correo.xoc.uam.mx.
authors: Camilo
authors: C
authors: Ríos
authors: Biological Systems Department, Autonomous Metropolitan University-Xochimilco, Calzada del Hueso 1100, Villa Quietud, Coyoacán, Mexico 04960, D.F., Mexico. Electronic address: syriverama@conacyt.mx.
authors: Susana
authors: S
authors: Rivera-Mancía
mesh_terms: D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005973:Glutamine; D002034:Bumetanide; D000641:Ammonia
keywords: Ammonia; Bumetanide; Bumetanide (PubChem CID: 2471); Glutamine; Hepatic encephalopathy; Liver damage; Manganese; ammonium acetate (PubChem CID: 517165); glutamine (PubChem CID: 5961); manganous chloride (PubChem CID: 24480)