title: Responses in primary astrocytes and C6-glioma cells to ammonium chloride and dibutyryl cyclic-AMP.
abstract: Elevated brain ammonia levels are a major factor in the genesis of hepatic encephalopathy (HE). The mechanism of ammonium chloride (NH4Cl) neurotoxicity involves interruption of oxidative metabolism. This leads to decreased levels of ATP concentration and subsequent glial fibrillary acidic protein (GFAP) degradation of astrocytes and fibrous C6-glioma cells. Our study investigates NH4Cl toxicity by evaluating changes in ATP concentration and mitochondrial function as well as by evaluating alterations in GFAP expression. NH4Cl induced decreases in ATP were detected after 15 minutes in C6-glioma cells and 24 hours in both cell types. Mitochondrial function, assessed by MTT (2-4,5-dimethylthiazol A-yl)-2, 5-diphenyltetrazolium bromide) assay, was impaired in both cell types at 24 hours following NH4Cl treatment. GFAP was also significantly decreased in both cell types. Morphologic and metabolic toxicities were greater in C6-glioma cells. The data clearly indicate that NH4Cl interrupts oxidative metabolism. The greater toxicity seen in C6-glioma cells may be due to their greater dependence on oxidative metabolism. Lastly, the decrease in GFAP is probably a consequence of diminished ATP.
authors.affiliation: Department of Cell Biology and Anatomy, Finch University of Health Sciences, The Chicago Medical School, North Chicago, IL 60064, USA.
authors.forename: N
authors.initials: N
authors.lastname: Haghighat
authors.forename: D W
authors.initials: DW
authors.lastname: McCandless
authors.forename: P
authors.initials: P
authors.lastname: Geraminegad
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000643:Ammonium Chloride; D003994:Bucladesine