Glucose-lowering effect of beta-phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes.
Following beta-phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with beta-phenylpyruvate and their blood glucose determined and brain histology assessed. beta-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent beta-phenylpyruvate-induced hypoglycemic events.
Gazit
Vered
V
Laboratory for Anesthesia, Pain and Neural Research, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Ben-Abraham
Ron
R
Rudin
Michael
M
Katz
Yeshayahu
Y
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D007003:Hypoglycemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D051379:Mice; D008813:Mice, Inbred ICR; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010661:Phenylketonurias / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010667:Phenylpyruvic Acids / Q000378:metabolism* / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D015996:Survival Rate
D001786:Blood Glucose; D007328:Insulin; D010667:Phenylpyruvic Acids; D005947:Glucose; C031606:phenylpyruvic acid