Short communication Intravenous toxicity of fructose-1,6-bisphosphate in rats Fernanda Bordignon Nunes, Patrick Barcelos Gaspareto, Roberto Christ Vianna Santos, Ma ´rcio de Assis, Ca ´ssio Meyer Graziottin, Vanderlei Biolchi, Jose ´ Carlos Farias Alves Filho, Adroaldo Lunardelli, Luı ´s D. A ´ vila, Melissa Guerra Simo ˜ es Pires, Paulo Harald Wa ¨chter, Jarbas Rodrigues De Oliveira * Laborato ´rio de Pesquisa em Biofisica, Departamento de Cie ˆncias Fisiolo ´gicas, Faculdade de Biocie ˆncias, Pontificia Universidade Cato ´lica do Rio Grande do Sul, Av. Ipiranga, 6681-Pre ´dio 12C-Sala 263-C.P. 1429 Porto Alegre, RS, Brazil Received 9 September 2002; received in revised form 3 January 2003; accepted 6 January 2003 Abstract Fructose-1,6-bisphosphate (FBP) is a bisphosphorilated sugar with a protective action against events that lead to cellular damage. The toxicity of the drug was assessed when administered intravenously in Wistar rats in doses of between 250 and 4000 mg/kg. Ionic calcium, total calcium, inorganic serum phosphate and the electrocardiographic profile of these animals were assessed. The lethal dose (LD 50 ) was established by means of PROBIT processing. There was no reduction in the levels of total calcium, with the administration of increased doses of FBP, although there was a significant reduction in the levels of ionic calcium in those groups that received 250 mg/kg and over. The serum phosphate showed a significant statistical increase in those groups that received 750 mg/kg and over. The LD 50 obtained in 24 h was 1068 mg/kg. Though it was not possible to elucidate the toxic mechanism of FBP, the electrocardiogram (ECG) showed that all the rats died of cardiac arrest. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Fructose-1,6-bispbosphate; Toxicity; LD 50 ; PROBIT 1. Introduction Fructose-1,6-bisphosphate (FBP), a high-energy intermediate metabolite of glycolysis (Kirttley and McKay, 1977), has been used therapeutically to attenuate the effects of ischemic injury in the kidney (Didlake et al., 1985), heart (Lazzarino et al., 1991), liver (Nakai et al., 1991), intestine (Sun et al., 1990), brain (Farias et al., 1990) and lung (Chu et al., 2002). De Oliveira et al. (1992) also have demonstrated that the simultaneous administration of galacto- samine and FBP prevents the hepatitis induced by galactosamine, diminishing the fall in the energy charge and preventing liver cell death. This action of FBP is specific and not shared by other phosphorylated sugars such as glucose-6-phos- * Corresponding author. Tel.:  /55-51-3320-3500x4147; fax:  /55-51-3320-3612. E-mail address: jarbas@pucrs.br (J.R. De Oliveira). Toxicology Letters 143 (2003) 73  /81 www.elsevier.com/locate/toxlet 0378-4274/03/$ - see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0378-4274(03)00075-4