title: Fructose 1,6-diphosphate augments paraquat injury in isolated dog lungs.
abstract: Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridylium dichloride), a widely used herbicide, causes pulmonary edema by a cyclic oxidation and reduction reaction with oxygen molecules with the production of oxygen free radicals. Because fructose 1,6-diphosphate (FDP) has recently been shown to inhibit the generation of oxygen free radicals by activated neutrophils, we determined the effects of FDP on PQ-induced increase in microvascular permeability in isolated blood-perfused dog lungs. Vascular permeability was assessed using the capillary filtration coefficient (Kf,c) and isogravimetric capillary pressure (Pc,i). There was no change in these variables over 5 h in the control lungs treated with saline (n = 5). A significant increase in Kf,c and a decrease in Pc,i, both of which indicated increased vascular permeability, were observed at 5 h of perfusion with 4 x 10(-3) M PQ (n = 5). Unexpectedly, an increase in microvascular permeability occurred within 4 h after administration of PQ in the lungs that were pretreated with FDP (2.7-14.2 mM, n = 6). Moreover the increases of Kf,c in the FDP-pretreated lungs were significantly greater than those in the lungs treated with PQ alone. Also, the final-to-initial lung weight ratio of the FDP-pretreated group was greater than those of the other groups. Thus the FDP dose used in the present study accentuated rather than prevented the PQ lung injury.
authors.affiliation: Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shibamoto
authors.forename: J C
authors.initials: JC
authors.lastname: Parker
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004285:Dogs; D004357:Drug Synergism; D005609:Free Radicals; D005635:Fructosediphosphates / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D010100:Oxygen / Q000378:metabolism; D010269:Paraquat / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D005609:Free Radicals; D005635:Fructosediphosphates; C029063:fructose-1,6-diphosphate; D010269:Paraquat; D010100:Oxygen