title: Toxicity of fructose-1,6-bisphosphate in developing normoxic rats.
abstract: Giving 500 mg/kg of fructose-1,6-bisphosphate intraperitoneally decreases hypoxic/ischaemic CNS injury of neonatal rats. Before administering fructose-1,6-bisphosphate to human neonates, its toxicity must be determined in neonatal animals. Thus, saline or 4,000, 6,000, or 8,000 mg/kg of fructose-1,6-bisphosphate was given intraperitoneally to normoxic 7 days old rats. One, 2, and 24 hr and 7 days later, blood Ca2+, PO(4)3-, blood urea nitrogen, and creatinine concentrations, and aspartate aminotransferase activity were measured. Organ pathology was determined at necropsy. Pups receiving 4,000 mg/kg of fructose-1,6-bisphosphate survived without evidence of injury or toxicity. All animals receiving 8,000 mg/kg and 27 percent of those receiving 6,000 mg/kg of fructose-1,6-bisphosphate died. Surviving fructose-1,6-bisphosphate-treated animals grew at the same rates and had similar weights as saline-treated animals. Nineteen percent of pups given 6,000 or 8,000 mg/kg of fructose-1,6-bisphosphate had mild perivascular fluid cuffing and/or microscopic pulmonary haemorrhage, but none of the animals given 4,000 mg/kg of the compound had evidence of injury. No other organ pathology was found in any of the animals. Renal and hepatic function were normal in all animals. Fructose-1,6-bisphosphate administration was associated with a significant increase in the fructose-1,6-bisphosphate concentration of blood. Administering 4,000 to 8,000 mg/kg of fructose-1,6-bisphosphate significantly decreased Ca2+ concentrations and increased PO(4)3- concentrations 1 and 2 hrs after fructose-1,6-bisphosphate administration. Similar changes in Ca2+ and PO(4)3- concentrations occurred after the administration of 10 mmol/kg of sodium phosphate. The wide margin of safety for fructose-1,6-bisphosphate (8 times the dose needed to prevent or reduce CNS injury) may render fructose-1,6-bisphosphate safe for use in neonates.
authors: Department of Paediatrics (Neonatology), University of California, San Francisco, USA.
authors: Z
authors: Z
authors: Vexler
authors: M
authors: M
authors: Berrios
authors: P C
authors: PC
authors: Ursell
authors: A
authors: A
authors: Sola
authors: D M
authors: DM
authors: Ferriero
authors: G A
authors: GA
authors: Gregory
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000097:blood / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D005635:Fructosediphosphates