86 research outputs found
Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute renal failure
BACKGROUND: In acute renal failure, a pronounced net protein catabolism occurs that has long been associated with corticoid action. By competitively blocking the glucocorticoid receptor with the potent antiglucocorticoid RU 38486, the present study addressed the question to what extent does corticoid action specific to uremia cause the observed muscle degradation, and does inhibition of glucocorticoid action reduce the protein wasting? METHODS: RU 38486 was administered in a dose of 50 mg/kg/24 h for 48 h after operation to fasted bilaterally nephrectomized (BNX) male adult Wistar rats and sham operated (SHAM) controls. Protein turnover was evaluated by high performance liquid chromatography (HPLC) of amino acid efflux in sera from isolated perfused hindquarters of animals treated with RU 38486 versus untreated controls. RESULTS: Administration of RU 38486 reduces the total amino acid efflux (TAAE) by 18.6% in SHAM and 15.6% in BNX and efflux of the indicator of net protein turnover, phenylalanine (Phe) by 33.3% in SHAM and 13% in BNX animals as compared to the equally operated, but untreated animals. However, the significantly higher protein degradation observed in BNX (0.6 ± 0.2 nmol/min/g muscle) versus SHAM (0.2 ± 0.1 nmol/min/g muscle) rats, as demonstrated by the marker of myofribrillar proteolytic rate, 3-Methylhistidine (3 MH) remains unaffected by administration of RU 38486 (0.5 ± 0.1 v. 0.2 ± 0.1 nmol/min/g muscle in BNX v. SHAM). CONCLUSION: RU 38486 does not act on changes of muscular protein turnover specific to uremia but reduces the effect of stress- stimulated elevated corticosterone secretion arising from surgery and fasting. A potentially beneficial effect against stress- induced catabolism in severe illness can be postulated that merits further study
Muscle protein breakdown rates in humans based on Nτ-methylhistidine (3-methylhistidine) content of mixed proteins in skeletal muscle and urinary output of Nτ-methylhistidine
Quantitative contribution by skeletal muscle to elevated rates of whole-body protein breakdown in burned children as measured by Nτ-methylhistidine output
Decrease of 3-methylhistidine and increase of NG,NG-dimethylarginine in the urine of patients with muscular dystrophy
Effect of corticosterone and its route of administration on muscle protein breakdown, measured in vivo by urinary excretion of Nτ-methylhistidine in rats: Response to different levels of dietary protein and energy
A rapid, sensitive method for the determination of 3-methylhistidine levels in urine and plasma using high-pressure liquid chromatography
- …