Pentoxifylline acutely reduces protein catabolism in chronically uremic patients.
BACKGROUND
We investigated the ability of pentoxifylline, a drug with hemorheological actions known to block tumor necrosis factor-alpha (TNF-alpha) release, to modulate whole-body protein kinetics in undialyzed patients with chronic uremia.


METHODS
Leucine rate of appearance (Ra) from proteolysis and leucine oxidation, a marker of net protein loss, were determined by infusing l-[1-13C]leucine and using the reciprocal pool model for calculations.


RESULTS
Intravenous infusion of pentoxifylline in the postabsorptive state (1 mg/kg within 3 hours) decreased the intracellular leucine Ra from proteolysis by -16% +/- 4% versus -3% +/- 2% of saline (P = 0.02) and leucine oxidation by -16% +/- 4% versus +4% +/- 2% of saline (P = 0.003). Combined infusions of pentoxifylline and a balanced amino acid mixture (0.2 mg/kg/min) decreased whole-body proteolysis by -53% +/- 7% versus -26% +/- 6% of amino acid infusion alone (P = 0.02). Circulating levels of TNF-alpha and TNF-alpha soluble receptors (sTNF-Rs) were elevated (P < 0.001) in patients compared with healthy controls. Pentoxifylline infusion did not significantly affect TNF-alpha levels, but decreased sTNF-Rs both in the postabsorptive state and during hyperaminoacidemia.


CONCLUSIONS
Pentoxifylline acutely decreased whole-body proteolysis in chronically uremic patients. Potential explanations for these pharmacological effects may include downregulation of the TNF-alpha system or other mechanisms related to the rheological action of the drug (eg, increased amino acid or insulin delivery to target cells).
Biolo
Gianni
G
Department of Clinical, Morphological, and Technological Sciences, Division of Internal Medicine, University of Trieste, Italy. biolo@units.it
Ciocchi
Beniamino
B
Bosutti
Alessandra
A
Situlin
Roberta
R
Toigo
Gabriele
G
Guarnieri
Gianfranco
G
D000596:Amino Acids / Q000097:blood; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000097:blood; D002908:Chronic Disease; D004334:Drug Administration Schedule; D005260:Female; D006401:Hematologic Agents / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011506:Proteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014511:Uremia / Q000188:drug therapy* / Q000209:etiology
D000596:Amino Acids; D002247:Carbon Isotopes; D006401:Hematologic Agents; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D007930:Leucine; D010431:Pentoxifylline