Toxicity of fructose-1,6-bisphosphate in developing normoxic rats

Giving 500 mg/kg of fructose-1,6-bisphosphate intraperitoneally decreases h ypoxic/ischaemic CNS injury of neonatal rats. Before administering fructose -1,6-bisphosphate to human neonates, its toxicity must be determined in neo natal 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+, PO43-, blood urea nitrogen, and creatinine concentrations, and aspartate aminotransferase activity were me asured. Organ pathology was determined at necropsy. Pups receiving 4,000 mg /kg of fructose-1,6-bisphosphate survived without evidence of injury or tox icity. 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-bisph osphate-treated animals grew at the same rates and had similar weights as s aline-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 mic roscopic pulmonary haemorrhage, but none of the animals given 4,000 mg/kg o f the compound had evidence of injury. No other organ pathology was found i n any of the animals. Renal and hepatic function were normal in all animals . Fructose-1,6-bisphosphate administration was associated with a significan t increase in the fructose-1,6-bisphosphate concentration of blood. Adminis tering 4,000 to 8, 000 mg/kg of fructose-1,6-bisphosphate significantly dec reased Ca2+ concentrations and increased PO43- concentrations 1 and 2 hrs a fter fructose-1,6-bisphosphate administration. Similar changes in Ca2+ and PO43- concentrations occurred after the administration of 10 mmol/kg of sod ium phosphate. The wide margin of safety for fructose-1,6-bisphosphate (8 t imes the dose needed to prevent or reduce CNS injury) may render fructose-1 ,6-bisphosphate safe for use in neonates.