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Titolo:
EFFECTS OF DILTIAZEM ON NETILMICIN-INDUCED NEPHROTOXICITY IN RABBITS
Autore:
LORTHOLARY O; BLANCHET F; NOCHY D; HEUDES D; SETA N; AMIRAULT P; CARBON C;
Indirizzi:
HOP BROUSSAIS,DEPT PATHOL,UER XAVIER BICHAT,INSERM,U13 F-75674 PARIS 14 FRANCE HOP BROUSSAIS,DEPT PATHOL,UER XAVIER BICHAT,INSERM,U13 F-75674 PARIS 14 FRANCE HOP BICHAT,DEPT PHARM F-75877 PARIS 18 FRANCE HOP BICHAT,DEPT BIOCHEM A F-75877 PARIS 18 FRANCE HOP BROUSSAIS,INSERM,U28 F-75674 PARIS 14 FRANCE HOP BROUSSAIS,DEPT PATHOL,UER XAVIER BICHAT,INSERM,U251 F-75674 PARIS14 FRANCE
Titolo Testata:
Antimicrobial agents and chemotherapy
fascicolo: 9, volume: 37, anno: 1993,
pagine: 1790 - 1798
SICI:
0066-4804(1993)37:9<1790:EODONN>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE-RENAL-FAILURE; AMINOGLYCOSIDE NEPHROTOXICITY; GENTAMICIN; CALCIUM; RATS; BLOCKERS; ISCHEMIA; LLC-PK1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
O. Lortholary et al., "EFFECTS OF DILTIAZEM ON NETILMICIN-INDUCED NEPHROTOXICITY IN RABBITS", Antimicrobial agents and chemotherapy, 37(9), 1993, pp. 1790-1798

Abstract

Aminoglycoside nephrotoxicity remains a common clinical problem and is the major cause of acute toxic renal failure in hospitalized patients. In recent studies, calcium channel blockers gave controversial results in the prevention of acute ischemic or toxic renal failure. The aims of the study were (i) to describe a rabbit model of mild renal failure (50% reduction in glomerular filtration rate with a mean value of 1.78 +/- 0.46 ml/kg/min) induced by netilmicin given intramuscularly at 20 mg/kg of body weight every 8 h for 5 days, (ii) to investigate the protective effect of diltiazem given at a therapeutic dose (1 mg/kg given intramuscularly every 8 h for 5 days), and (iii) to investigate the mechanisms of this protection through evaluation of function tests, optic histology, and glomerular morphometry. Animals treated with netilmicin and diltiazem exhibited an unchanged glomerular filtration rate compared with controls (3.39 +/- 0.58 versus 3.68 +/- 0.78 ml/kg/min, respectively). This protective effect was not associated with any change in systemic or renal hemodynamics (i.e., no change in renal plasma flow) or changes in the pharmacokinetics of netilmicin, as assessedby fractional excretion and cortical uptake. Netilmicin-induced tubular toxicity was unchanged by diltiazem. Our results suggest that (i) netilmicin exhibits a toxic effect at both the glomerular and the tubular levels, (ii) diltiazem, a calcium channel blocker, when given at low therapeutic doses, is able to prevent the aminoglycoside-induced renal failure through a potential glomerular mechanism. The precise mechanisms of the protection remain to be elucidated. These results deserveclinical evaluation in high-risk patients.

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Documento generato il 30/11/20 alle ore 18:45:08