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Titolo:
Gender differences in the potentiation of N-(3,5-dichlorophenyl)succinimide metabolite nephrotoxicity by phenobarbital
Autore:
Hong, SK; Anestis, DK; Valentovic, MA; Ball, JG; Brown, PI; Rankin, GO;
Indirizzi:
Marshall Univ, Sch Med, Dept Pharmacol, Huntington, WV 25704 USA Marshall Univ Huntington WV USA 25704 Pharmacol, Huntington, WV 25704 USA Marshall Univ, Sch Med, Dept Anat, Huntington, WV 25755 USA Marshall UnivHuntington WV USA 25755 Dept Anat, Huntington, WV 25755 USA
Titolo Testata:
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A
fascicolo: 3, volume: 64, anno: 2001,
pagine: 241 - 256
SICI:
1528-7394(20011012)64:3<241:GDITPO>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIC IMIDE COMPOUNDS; ACID 2-NDHSA NEPHROTOXICITY; GLUTATHIONE S-TRANSFERASES; FISCHER 344 RATS; BIOLOGICAL-ACTIVITY; SPRAGUE-DAWLEY; N-(3,5-DICHLOROPHENYL)-2-HYDROXYSUCCINIMIDE NDHS; BUTHIONINE SULFOXIMINE; ANTIMICROBIAL ACTIVITY; HISTOLOGICAL PATTERN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Rankin, GO Marshall Univ, Sch Med, Dept Pharmacol, 1542 Spring Valley Dr, Huntington,WV 25704 USA Marshall Univ 1542 Spring Valley Dr Huntington WV USA 25704 USA
Citazione:
S.K. Hong et al., "Gender differences in the potentiation of N-(3,5-dichlorophenyl)succinimide metabolite nephrotoxicity by phenobarbital", J TOX E H A, 64(3), 2001, pp. 241-256

Abstract

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces acute nephrotoxicity characterized as polyuric renal failure with proximal tubular necrosis. Phenobarbital pretreatment potentiates NDPS and N-(3,5-dichlorophenyl)-2-hydroxy-succinimide (NDHS, a nephrotoxic metabolite of NDPS) nephrotoxicity in male rats, The purpose of this study was to determinethe ability of phenobarbital pretreatment to potentiate (1) NDHS nephrotoxicity in female rats and (2) N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA, a nephrotoxic metabolite of NDHS) nephrotoxicity in male and female rats. Age-matched male and female Fischer 344 rats (4/group) were pretreated intraperitoneally (ip) with phenobarbital (75 mg/d, 3 d). At 24 h after the last injection of phenobarbital, an ip injection of NDHS (0.025 mmol/kg), 2-NDHSA (0.025 mmol/kg, females; 0.05 mmol/kg, males), or vehicle was given and renal function tvas monitored at 24 and 48 h post NDPS metabolite or vehicle. Additional groups received the NDPS metabolite or vehicle only and were also monitored for 48 h. In a separate experiment, male Fischer344 rats were pretreated with piperonyl butoxide (PIBX, 1360 mg/kg) or thcPIBX vehicle. 2-NDHSA (0.1 mmol/kg) or vehicle was administered (ip) 30 min after PIBX, and renal function was monitored for 24 h. Phenobarbital markedly potentiated 2-NDHSA nephrotoxicity in male rats as evidenced by increased kidney weight, increased blood urea nitrogen (BUN) concentration, and decreased tetraethylammonium (TEA) accumulation by renal cortical slices. PIBX had no effect on 2-NDHSA nephrotoxicity. Phenobarbital pretreatment did not markedly enhance the nephrotoxic potential of NDHS or 2-NDHSA in femalerats. These results indicate that phenobarbital exhibits differential potentiation of NDPS metabolite nephrotoxicity in male and female rats and thatthe potentiation of 2-NDHSA nephrotoxicity observed in males is not due tocytochrome P-450-mediated oxidative biotransformation.

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Documento generato il 06/04/20 alle ore 22:45:09