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Titolo:
THE EFFECT OF SILIBININ ON EXPERIMENTAL CYCLOSPORINE NEPHROTOXICITY
Autore:
ZIMA T; KAMENIKOVA L; JANEBOVA M; BUCHAR E; CRKOVSKA J; TESAR V;
Indirizzi:
CHARLES UNIV,FAC MED 1,INST MED CHEM & BIOCHEM 1,KATERINSKA 32 CS-12000 PRAGUE 2 CZECH REPUBLIC
Titolo Testata:
Renal failure
fascicolo: 3, volume: 20, anno: 1998,
pagine: 471 - 479
SICI:
0886-022X(1998)20:3<471:TEOSOE>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED LIPID-PEROXIDATION; HUMAN LIVER-MICROSOMES; RAT; EXPRESSION; ENDOTHELIN;
Keywords:
CYCLOSPORINE; SILIBININ; NEPHROTOXICITY; LIPID PEROXIDATION; MALONDIALDEHYDE; P450;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
T. Zima et al., "THE EFFECT OF SILIBININ ON EXPERIMENTAL CYCLOSPORINE NEPHROTOXICITY", Renal failure, 20(3), 1998, pp. 471-479

Abstract

The immunosuppressive drug cyclosporine A (CsA), is metabolized by cytochrome P-450 IIIA. It causes acute reversible as well as chronic largely irreversible nephrotoxic effects. This effect is bases on vasoconstriction of the afferent and efferent glomerular arterioles which leads to a reduction in glomerular plasma flow and glomerular filtration rate. The mechanisms of the vasoconstriction are unclear with a numberof different pathways under discussion. Silibinin is the main constituent of silymarin. Silibinin inhibits lipid peroxidation on hepatic microsomes and mitochondria of rats and is also able to reduce the activity of various monooxygenases. Cyclosporin-induced lipid peroxidation and affected cytochrome P-450 may even contribute to cyclosporine nephrotoxicity. We examined the possibility that silibinin had a protective effect as a result of its radical scavenging properties. Silibinin, 5 mg/kg BW i.p., was administered 30 min before cyclosporine application at dose of 30 mg/kg BW daily i.p. The biochemical parameters, totalmalondialdehyde (MDA) in whole blood and kidney homogenates and specific content of cytochrome P-450 in microsomal liver suspension were estimated Three groups were studied: controls (con), cyclosporine alone (CsA), and cyclosporien plus silibinin (CsA + Sili). Creatinine was significantly increased after 2 weeks in both cyclosporine treated groups compared to controls (CsA 60.2 +/- 10.6 versus 45.8 +/- 10.4 mu mol/L, p < 0.05; and CsA + Sili 72.0 +/- 8.3 versus 45.8 +/- 10.4 mu mol/L, p < 0.001) and glomerular filtration rate (GFR) was significantly decreased (p < 0.0001) in the same groups. Total MDA,vas elevated only in CsA rats (2.26 +/- 0.35 mu mol/L, p < 0.05) in comparison with controls (1.60 +/- 0.44 mu mol/L, p < 0.05) and with rats treated by CsA + Sili (1.65 +/- 0.27 mu mol/L, p < 0.05). The specific content of cytochrome P-450 in microsomal liver suspension was increased in group CsA Sili (1.179 +/- 0.115 nmol/mg prot) compared to control group (0.775+/- 0.086 nmol/mg prot., p < 0.05) and also CsA group (0.806 +/- 0.098 nmol/mg prot., p < 0.05). In conclusion, silibinin decreased cyclosporine-induced lipid peroxidation without a protective effect on GFR. These data indicate that this pathway is not be important in cyclosporine-induced nephrotoxicity. Administration of both drugs (CsA + sili) increased the specific content of cytochrome P-450 in liver microsomes. This suggests that the effect of silibinin on cyclosporine biotransformation in the liver is via cytochrome P-450.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:11:24