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. CONCLUSION: 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). Copyright 2002 by the National Kidney Foundation, Inc.
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. CONCLUSION: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). Copyright 2002 by the National Kidney Foundation, Inc.
Authors: Serpil Muge Deger; Adriana M Hung; Charles D Ellis; Cindy Booker; Aihua Bian; Guanhua Chen; Naji N Abumrad; T Alp Ikizler Journal: Clin J Am Soc Nephrol Date: 2016-06-08 Impact factor: 8.237