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Titolo:
TARGETING NAPROXEN COUPLED TO HUMAN SERUM-ALBUMIN TO NONPARENCHYMAL CELLS REDUCES ENDOTOXIN-INDUCED MORTALITY IN RATS WITH BILIARY-CIRRHOSIS
Autore:
ALBRECHT C; MEIJER DKF; LEBBE C; SAGESSER H; MELGERT BN; POELSTRA K; REICHEN J;
Indirizzi:
UNIV BERN,DEPT CLIN PHARMACOL,MURTENSTR 35 CH-3010 BERN SWITZERLAND UNIV BERN,DEPT CLIN PHARMACOL CH-3010 BERN SWITZERLAND UNIV GRONINGEN,DEPT PHARMACOKINET & DRUG DELIVERY GRONINGEN NETHERLANDS
Titolo Testata:
Hepatology
fascicolo: 6, volume: 26, anno: 1997,
pagine: 1553 - 1559
SICI:
0270-9139(1997)26:6<1553:TNCTHS>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; RENAL-FUNCTION; KUPFFER CELLS; LIVER-DISEASE; HYPERDYNAMIC CIRCULATION; FACTOR-ALPHA; DRUGS; INJURY; PROSTAGLANDIN; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
51
Recensione:
Indirizzi per estratti:
Citazione:
C. Albrecht et al., "TARGETING NAPROXEN COUPLED TO HUMAN SERUM-ALBUMIN TO NONPARENCHYMAL CELLS REDUCES ENDOTOXIN-INDUCED MORTALITY IN RATS WITH BILIARY-CIRRHOSIS", Hepatology, 26(6), 1997, pp. 1553-1559

Abstract

Endotoxin is thought to play a major role in cirrhotic liver disease,Cyclo-oxygenase inhibitors were shown to be partially protective against endotoxin but cannot be used in cirrhotic patients because of renal side-effects, We argued that administration of naproxen (NAP) linkedto human serum albumin (HSA), which results in specific delivery of NAP to endothelial cells (EC) and Kupffer cells (KC) and exhibited hepatoprotective effects against Lipopolysaccharide (LPS) in vitro, could protect cirrhotic rats from LPS toxicity while preserving renal function. The studies were performed in rats rendered cirrhotic by bile ductligation (BDL); animals received LPS (Escherichia coli, 800 mu g/kg) intravenously. Five groups were studied: LPS alone, rats pretreated with a conventional dose of NAP (50 mg/kg), NAP-HSA (22 mg/kg), NAP equimolar to NAP-HSA (50 mg/kg), or the HSA carrier. LPS induced significant mortality (55%); this was not affected by equimolar NAP (57%) but accentuated by conventional NAP (88%), In contrast, NAP-HSA provided significant protection (9%; P < .05). After conventional NAP treatment, significant renal toxicity was observed as evidenced by a marked reduction in sodium excretion (LPS vs. NAP-HSA vs, NAP [SO mg/kg] 33 +/- 22vs, 50 +/- 39 vs. 4 +/- 3 mu mol/h; P < .05). Renal prostaglandin E-2(PGE(2)) excretion was reduced by NAP in all groups, but most markedly at the conventional dosage (LPS vs. NAP-HSA vs, NAP [50 mg/kg] 132 +/- 115 vs. 39 +/- 19 vs, 9 +/- 8 ng/mL; P < .05). Successful targetingwas evidenced by a significant hepatic enrichment of NAP in the NAP-HSA group compared with the equimolar untargeted group (30.16 +/- 9.33 vs. 1.13 +/- 1.95 nmol/g liver). Thus, targeting NAP to EC/KC results in improved survival, higher efficacy, and sparing of renal function in cirrhotic rats.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 11:24:51