Effect of succinimide ring modification on N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in sprague-dawley and fischer 344 rats

Yang, David J.; Richmond, Cathy D.; Teets, Vonda J.; Brown, Patrick I.; Rankin, Gary O.

doi:10.1016/0300-483x(85)90113-1

Cited by 32 publications

(6 citation statements)

References 14 publications

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“…Diuresis, loss of body weight, proteinuria, and glucosuria were also seen in animals that received this dose. These changes are comparable to prior reports (Rankin, 1982;Rankin et al, 1984Rankin et al, , 1985Kellner-Weibel et al, 1995). We also found that ABT pretreatment effectively inhibited conversion of NDPS to nephrotoxic metabolites by the liver cells and prevented NDPS toxicity in vivo.…”

Section: Discussionsupporting

confidence: 80%

“…ARO, which is an inducer of the P450 1A and 2B isozyme families (Guengerich et al, 1982), also enhanced NDPS nephrotoxicity. The variability in BUN values obtained from rats that received 0.2 mmol/kg NDPS following pretreatment with PB or ARO (Table 1) may be due to the "steep" dose-response curve exhibited by NDPS in Fischer 344 rats (Rankin et al, 1985). Increasing the number of animals in these experiments failed to reduce this variability.…”

Section: Discussionmentioning

confidence: 71%

“…Email: p.harvis@pcps.edu. icity studies indicated that NDPS induces a nephrotic syndrome in rats that is similar to human interstitial nephritis (Sugihara et al, 1975;Barrett et al, 1983). In acute toxicity studies, NDPS produced diuresis, proteinuria, glucosuria, and elevated blood urea nitrogen; alterations in renal organic ion uptake and increased kidney weights were also reported (Rankin, 1982;Rankin et al, 1984Rankin et al, , 1985Kellner-Weibel et al, 1995). Sugihara et al (1975) suggested that NDPS is a potentially useful model compound for studying chemically induced interstitial nephritis.…”

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confidence: 99%

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Cytochrome P450-Mediated Metabolism and Nephrotoxicity of N-(3,5-Dichlorophenyl)succinimide in Fischer 344 Rats

1997

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The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is nephrotoxic in rats. Previous studies have suggested that oxidative hepatic biotransformation is required for the induction of kidney damage. The experiments described in this paper were designed to further investigate the relationship between NDPS metabolism and nephrotoxicity using various modulators of cytochrome P450 activity. Male Fischer 344 rats were pretreated with the P450 inducers Aroclor 1254 (ARO), isoniazid (INH), 3-methylcholanthrene (3-MC), and phenobarbital (PB), or the P450 inhibitor 1-aminobenzotriazole (ABT). Control animals received vehicle only. NDPS metabolism was investigated using hepatocytes isolated from the various treatment groups. Separate experiments were also conducted to evaluate the effects of these pretreatments on NDPS-induced nephrotoxicity in rats. PB and ARO enhanced formation of the known nephrotoxic NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide, N-(3,5-dichlorophenyl>2-hydroxysuccinamic acid, and iV-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid, by the hepatocytes. In contrast, ABT inhibited formation of the nephrotoxic metabolites, whereas INH and 3-MC did not alter NDPS biotransformation. NDPS-induced renal damage was potentiated by pretreating the rats with PB or ARO and was attenuated by ABT. Compared with control animals, toxicity was unaffected by INH or 3-MC pretreatments. Thus, there was a correlation between pretreatments that induce P450-mediated NDPS metabolism and the effects that these compounds have on NDPS-induced nephrotoxicity. The data indicate that specific P450 isozymes metabolize NDPS to its hydroxylated products and suggest that these metabolites mediate the nephrotoxicity induced by NDPS. © 1997 Sodtty of To iV-(3,5-Dichlorophenyl)succinimide (NDPS, Fig.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 71%

mentioning

confidence: 99%

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Cytochrome P450-Mediated Metabolism and Nephrotoxicity of N-(3,5-Dichlorophenyl)succinimide in Fischer 344 Rats

1997

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“…The role of the succinimide ring structure in N-arylsuccinimide-induced nephrotoxicity has also been examined. Using NDPS as the model nephrotoxicant, Yang et al (1985c) noted that addition of methyl groups to the succinimide ring, removal of one or both carbonyl groups, breaking the ethylene bridge, or hydrolysis of the succinimide ring each resulted in compounds with a much reduced potential to induce nephrotoxicity. Kellner-Weibel et al (1995) noted that if the ring size in NDPS is increased from five members (a succinimide) to six members (a glutarimide) by addition of a methylene unit, a compound was produced with minimal nephrotoxic potential compared to NDPS.…”

Section: Structure-nephrotoxicity Relationshipsmentioning

confidence: 99%

“…Harvison et al (1992) subsequently found that NDPHS and NDPHSA were nonnephrotoxicants in rats at doses up to 1 mmol/kg, ip, which supported aryl hydroxylation as a detoxification pathway. Similarly, hydrolysis of NDPS to NDPSA and/or 3,5-dichloroaniline appears to be a detoxification pathway as both metabolites are less potent nephrotoxicants than NDPS (Yang et al, 1985c;Rankin et al, 1986b) (Table 4). …”

Section: N-(35-dichlorophenyl)malonamic Acid (Dma) It Was Also Detementioning

confidence: 99%

Mobile Telephones and Cancer—a Review of Epidemiological Evidence

Kundi

Mild²,

Hardell

et al. 2004

Journal of Toxicology and Environmental Health, Part B

135

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There is considerable public concern about possible long-term adverse health effects of mobile phones. While there is scientific controversy about long-term health effects of high-frequency electromagnetic fields lasting for at least 50 yr, the rise and success of mobile telecommunication made it necessary to investigate the problem more comprehensively and assess the possible risk cautiously because never before in history has a substantial proportion of the population been exposed to microwaves in the near field and at comparably high levels. Because the mostly localized exposure target region is the head, most epidemiological studies focus on brain tumors. Overall nine epidemiological studies have been published, four from the United States, two from Sweden, and one each from Denmark, Finland, and Germany. Seven studies were mainly on brain tumors, with one investigating in addition to brain tumors salivary gland cancer and another cancer of the hematopoietic and lymphatic tissues, and one examining intraocular melanoma. All studies have some methodological deficiencies: (1) too short duration of mobile phone use to be helpful in risk assessment, (2) exposure was not rigorously determined, and (3) there is a possibility of recall and response error in some studies. Nevertheless, all studies approaching reasonable latencies found an increased cancer risk associated with mobile phone use. Estimates of relative risk in these studies vary between 1.3 and 4.6 with highest overall risk for acoustic neuroma (3.5) and uveal melanoma (4.2), and there is evidence for enhanced cancer risk with increasing latency and duration of mobile phone use.

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