title: Effect of pentoxifylline on nitrogen balance and 3-methylhistidine excretion in parenterally fed endotoxemic rats.
abstract: Pentoxifylline interrupts early gene activation for tumor necrosis factor, interleukin-1, and interleukin-6 production and improves survival from experimental sepsis. These effects can alter nitrogen loss during critical illness. To determine the dose-dependent influence of pentoxifylline on nitrogen loss, 44 male Sprague-Dawley rats (220 to 265 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (LPS) at 9 mg x kg(-1) x d(-1), or PN plus LPS plus a continuous infusion of pentoxifylline at either 25 (PEN25) or 100 mg x kg(-1) x d(-1) (PEN100) for 48 h. Before randomization, all animals underwent intravenous cannulation and 40 h of PN adaptation. All animals received isocaloric, isonitrogenous PN (160 kcal x kg(-1) x d(-1) and 1.0 gN x kg(-1) x d(-1)) and were kept nil per os except for water ad libitum. Administration of LPS significantly worsened nitrogen balance for all three groups compared with PN control; however, pentoxifylline only modestly improved nitrogen balance compared with LPS (206 +/- 255, -497 +/- 331, -332 +/- 329, and -310 +/- 383 mg/48hr for the PN, LPS, PEN25, and PEN100 groups, respectively; P < 0.001). Pentoxifylline did not significantly change 3-methylhistidine urinary excretion compared with LPS (573 +/- 180, 705 +/- 156, 780 +/- 326, and 683 +/- 266 microg/48 h for the PN, LPS, PEN25, and PEN100 groups, respectively, P not significant). Pentoxifylline, given in therapeutic doses after an endotoxin challenge, modestly, but not significantly, improved nitrogen balance. Urinary 3-methylhistidine excretion was not influenced by pentoxifylline. A dose-dependent effect by pentoxifylline on these markers was not evident.
authors.affiliation: Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. rdickerson@utmem.edu
authors.forename: R N
authors.initials: RN
authors.lastname: Dickerson
authors.forename: J F
authors.initials: JF
authors.lastname: Mouser
authors.forename: J T
authors.initials: JT
authors.lastname: Methvin
authors.forename: D A
authors.initials: DA
authors.lastname: Kuhl
authors.forename: E B
authors.initials: EB
authors.lastname: Hak
authors.forename: R O
authors.initials: RO
authors.lastname: Brown
authors.forename: L J
authors.initials: LJ
authors.lastname: Hak
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008762:Methylhistidines / Q000652:urine*; D009584:Nitrogen / Q000378:metabolism*; D010288:Parenteral Nutrition; D010431:Pentoxifylline / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides; D008762:Methylhistidines; C028118:3-methylhistidine; D009584:Nitrogen; D010431:Pentoxifylline