Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis

1993 ◽  
Vol 265 (4) ◽  
pp. E660-E666 ◽  
Author(s):  
D. Breuille ◽  
M. C. Farge ◽  
F. Rose ◽  
M. Arnal ◽  
D. Attaix ◽  
...  
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Acute Phase ◽  
Protein Metabolism ◽  
Muscle Wasting ◽  
Acute Phase Protein ◽  
Muscle Protein ◽  
Liver Protein ◽  
Phase Protein

Sepsis induces metabolic disorders that include loss of body weight, muscle wasting, and acute-phase protein synthesis in liver. Cytokines are generally recognized as active mediators of these disorders, and the implication of tumor necrosis factor (TNF) has been frequently discussed in the recent past. However, the identity of the active agent in alterations of protein metabolism is still controversial. To improve our understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolism in the following three groups of rats: infected control rats (INF-C); infected rats pretreated with pentoxifylline (PTX-INF), which is a potent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF group pretreated with pentoxifylline. Pentoxifylline nearly completely suppressed TNF secretion but did not influence the transient fall in rectal temperature, the decreased hematocrit, and the increased liver protein mass and synthesis observed in INF-C rats. Pentoxifylline decreased the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle protein synthesis induced by infection. The overall data indicate that pentoxifylline is an effective agent in mitigating the characteristic muscle protein wasting induced by sepsis and confirm the limited role of TNF in the mediation of the acute-phase protein synthesis. Our results suggest a probable implication of TNF in the regulation of protein balance in muscle but do not allow discarding possible implication of other mediators that would be inhibited by pentoxifylline.

Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients

2005 ◽  
Vol 15 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Guido Bellinghieri ◽  
Domenico Santoro ◽  
Menotti Calvani ◽  
Vincenzo Savica
Keyword(s):  
Protein Synthesis ◽  
Acute Phase ◽  
Acute Phase Protein ◽  
Hemodialysis Patients ◽  
Phase Protein

Altered protein metabolism following coronary artery bypass graft (CABG) surgery

2008 ◽  
Vol 114 (4) ◽  
pp. 339-346 ◽  
Author(s):  
Giuseppe Caso ◽  
James A. Vosswinkel ◽  
Peter J. Garlick ◽  
Mohamed K. Barry ◽  
Thomas V. Bilfinger ◽  
...  
Keyword(s):  
Body Weight ◽  
Cardiopulmonary Bypass ◽  
Protein Metabolism ◽  
Acute Phase Protein ◽  
Muscle Protein ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Artery Bypass Graft ◽  
Cabg Surgery ◽  
Phase Protein

The aim of the present study was to investigate the acute effect of CABG (coronary artery bypass graft) surgery on the rates of synthesis of muscle protein, the positive acute-phase protein fibrinogen and the negative acute-phase protein albumin. Synthesis rates of muscle protein, fibrinogen and albumin were measured simultaneously before and 4 h after the end of surgery from the incorporation of L-[2H5]phenylalanine (given at 43 mg/kg of body weight) in 12 patients undergoing CABG surgery. Surgery was performed either with the use of extracorporeal circulation with cardiopulmonary bypass (on-pump; n=5) or with the beating heart procedure without cardiopulmonary bypass (off-pump; n=7). Post-surgical muscle protein fractional synthesis rates were decreased by 36±6.5% compared with pre-surgical values (1.59±0.10 compared with 0.97±0.08%/day respectively; P<0.001). In contrast, the synthesis rates of both fibrinogen (36±4 compared with 100±11 mg·day−1·kg−1 of body weight; P<0.0001) and albumin (123±12 compared with 178±19 mg·day−1·kg−1 of body weight; P<0.001) were both significantly increased after surgery. No significant differences were found between surgery performed with or without cardiopulmonary bypass. In conclusion, the results demonstrate that CABG surgery has a profound effect on protein metabolism, with a differential response of protein synthesis in muscle and liver.

scholarly journals Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting

1998 ◽  
Vol 274 (6) ◽  
pp. R1518-R1525 ◽  
Author(s):  
Atsushi Kaibara ◽  
Armin Moshyedi ◽  
Troy Auffenberg ◽  
Amer Abouhamze ◽  
Edward M. Copeland ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Protein ◽  
Obese Mice ◽  
Preferential Loss ◽  
Phase Protein ◽  
Protein Response

The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-α as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (α1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.

Metabolic changes in rats during a continuous infusion of recombinant interleukin-1

1996 ◽  
Vol 270 (2) ◽  
pp. E305-E312 ◽  
Author(s):  
P. R. Ling ◽  
J. H. Schwartz ◽  
M. Jeevanandam ◽  
J. Gauldie ◽  
B. R. Bistrian
Keyword(s):  
Food Intake ◽  
Continuous Infusion ◽  
Acute Phase ◽  
Acute Phase Protein ◽  
Muscle Protein ◽  
Nitrogen Loss ◽  
Interleukin 1 ◽  
Matched Pair ◽  
Temperature Plasma ◽  
Phase Protein

The effects of recombinant interleukin-1 (IL-1), given as a continuous infusion for 6 days, on host responses were determined in rats. The development of fever, change in food intake and body weight, and key components of the acute-phase response in energy and protein metabolism were assessed. The effects of IL-1 were compared with those observed in a matched pair-fed group (semistarved), to distinguish the contribution from anorexia, and in a group that received IL-1 for 4 h acutely. IL-1 significantly increased core temperature, plasma levels of IL-6, and acute-phase protein production and decreased food intake and the circulating zinc level. The catabolic effects of IL-1 on nitrogen loss and muscle protein breakdown were independent of, and additive to those from malnutrition. The changes in energy expenditure, cumulative urinary nitrogen, and hydroxyproline excretion in the chronic IL-1 group were increased over semistarved animals. Finally, changes in muscle protein kinetics were only seen with chronic IL-1 infusion, and the changes in acute-phase protein were greater.

scholarly journals Acute Phase Protein Levels and Thymus, Spleen and Plasma Protein Synthesis Rates Differ in Adult and Old Rats

2003 ◽  
Vol 133 (1) ◽  
pp. 215-219 ◽  
Author(s):  
Isabelle Papet ◽  
Dominique Dardevet ◽  
Claire Sornet ◽  
Fabienne Béchereau ◽  
Jacques Prugnaud ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Acute Phase ◽  
Plasma Protein ◽  
Acute Phase Protein ◽  
Protein Levels ◽  
Phase Protein ◽  
Old Rats

Effect of the Cyclo-Oxygenase Inhibitor Fenbufen on Muscle and Liver Protein Metabolism, Muscle Glutamine and Plasma Insulin in Endotoxaemic Rats

1989 ◽  
Vol 77 (1) ◽  
pp. 13-20 ◽  
Author(s):  
M. M. Jepson ◽  
D. J. Millward
Keyword(s):  
Escherichia Coli ◽  
Protein Synthesis ◽  
Food Intake ◽  
Rectal Temperature ◽  
Protein Metabolism ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Liver Protein ◽  
Glutamine Concentration ◽  
Lps Treatment

1. The effect of fenbufen (γ-oxo-[1,1′-biphenyl]-4-butanoic acid), a known cyclo-oxygenase inhibitor, on the changes in muscle and liver protein metabolism in response to Escherichia coli endotoxin has been investigated in the rat. 2. Young male rats were fed a purified diet [18% (w/w) casein], with or without fenbufen (1.2 g/kg of diet). Groups of animals were injected with either endotoxin (LPS; Escherichia coli lipopolysaccharide 0.127 B8; 3 mg/kg body weight) or saline. Rectal temperature and food intake were measured over the following 24 h period, after which time measurements were made of muscle and liver protein content and synthesis in vivo, muscle protein degradation as the difference between protein synthesis and growth rates, muscle glutamine concentration and plasma insulin. 3. Fenbufen treatment alone tended to lower rectal temperature. It also reduced plasma insulin, slightly reduced food intake and slowed growth and muscle protein turnover, although muscle glutamine concentrations were unchanged. The slower protein synthesis mainly reflected reduced translational activity, which was consistent with the reduced insulin concentration. 4. LPS treatment increased rectal temperature by 1.6°C, and this was abolished by fenbufen, indicating that the dose of the drug was sufficient to block prostaglandin production in the hypothalamus. 5. LPS treatment induced similar losses in body weight and muscle protein in both control and fenbufen groups, despite a 50% lower food intake in the LPS plus fenbufen group compared with the LPS-only group. The loss of muscle protein in both groups reflected reduced protein synthesis and increased protein degradation. LPS treatment alone induced elevated plasma insulin, but fenbufen blocked this response and the insulin levels remained depressed. Muscle glutamine concentration fell in both LPS-treated groups, suggesting that the depression of protein synthesis and the development of the insulin resistance might be linked to the loss of intracellular glutamine. 6. LPS induced a relative increase in hepatic protein content, and total protein synthesis (by approximately 40%); fenbufen had no influence on these responses. 7. It is concluded that whereas treatment with fenbufen has marked effects on plasma insulin concentration, it has no influence on muscle and liver protein metabolism during endotoxaemia. Alternative mechanisms to those involving prostaglandins as mediators of the catabolic response of muscle are discussed, including those involving the glutamine transporter.

scholarly journals Protein metabolism in the tumour-bearing mouse. Rates of protein synthesis in host tissues and in an Ehrlich ascites tumour at different stages in tumour growth

1989 ◽  
Vol 264 (3) ◽  
pp. 713-719 ◽  
Author(s):  
M N Lopes ◽  
P Black ◽  
A J Ashford ◽  
V M Pain
Keyword(s):  
Protein Synthesis ◽  
Food Intake ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Liver Protein ◽  
Humoral Factors ◽  
Ascites Tumour ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour

We have investigated the time course of the changes in protein metabolism in skeletal muscle and liver in mice during the progression of growth of an Ehrlich ascites tumour. The rate of protein synthesis in muscle begins to fall very rapidly, and the decrease is clearly established by the time the tumour first becomes visible at 4 days after implantation of the cells. Liver protein synthesis increases substantially, and protein breakdown in muscle increases, but the onset of both these changes occurs later than the fall in muscle protein synthesis. A decrease in food intake in these animals occurs very rapidly after introduction of the cells. The fractional rate of protein synthesis in the tumour cells falls from 73%/day at 5 days to 26%/day at 12 days after injection, but on an absolute basis the rate of protein synthesis in the tumour at 5 days of growth is very small compared with that in muscle and liver. These results are consistent with the notion that the initial effects on muscle protein synthesis and food intake are brought about by humoral factors rather than as direct consequences of the metabolic demands of the growing tumour.

Sign in / Sign up

Export Citation Format

Share Document