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).


CONCLUSIONS
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.
Mondry
Adrian
A
Bioinformatics Institute, 30 Biopolis Street, #07-01 Matrix Building, 138671 Singapore. mondry@hotmail.com
D000138:Acidosis / Q000209:etiology; D058186:Acute Kidney Injury / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D008762:Methylhistidines / Q000097:blood; D015735:Mifepristone / Q000494:pharmacology*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009392:Nephrectomy; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000378:metabolism
D000596:Amino Acids; D005938:Glucocorticoids; D006727:Hormone Antagonists; D008762:Methylhistidines; D009124:Muscle Proteins; D015735:Mifepristone; C028118:3-methylhistidine
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