Abstract |
N-(3,5-Dichlorophenyl)succinimide ( NDPS) is an agricultural fungicide which induces acute tubular necrosis as its primary toxicity. Two NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide ( NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid ( NDHSA) previously have been shown to be more potent nephrotoxicants than NDPS. In addition, buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, was found to attenuate NDPS-induced nephrotoxicity. The purpose of this study was to examine the effects of BSO pretreatment on NDHS- and NDHSA-induced nephrotoxicity. Male Fischer-344 rats (4 rats/group) were administered intraperitoneally (i.p.) BSO (890 mg/kg) 2 h before NDHS or NDHSA (0.1 or 0.2 mmol/kg, i.p.) or vehicle ( sesame oil, 2.5 ml/kg), and renal function monitored at 24-h intervals for 48 h. BSO pretreatment markedly attenuated NDHSA (0.1 or 0.2 mmol/kg)-induced effects on the renal functional parameters monitored. BSO pretreatment also markedly reduced NDHS (0.1 mmol/kg)-induced renal effects. However, NDHS (0.2 mmol/kg) nephrotoxicity was attenuated to a lesser extent than NDHS (0.1 mmol/kg) nephropathy. These results indicate that glutathione is an important mediator of NDPS metabolite nephrotoxicity and suggests that BSO did not attenuate NDPS nephropathy by inhibiting NDPS biotransformation to NDHS or NDHSA.
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Authors | G O Rankin, V J Teets, D W Nicoll, P I Brown |
Journal | Toxicology letters
(Toxicol Lett)
Vol. 57
Issue 3
Pg. 297-308
(Aug 1991)
ISSN: 0378-4274 [Print] Netherlands |
PMID | 1882389
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Fungicides, Industrial
- Succinates
- Succinimides
- N-(3,5-dichlorophenyl)-2-hydroxysuccinimide
- Methionine Sulfoximine
- Buthionine Sulfoximine
- N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid
- Glutathione
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Topics |
- Animals
- Buthionine Sulfoximine
- Fungicides, Industrial
(toxicity)
- Glutathione
(physiology)
- Kidney
(drug effects)
- Male
- Methionine Sulfoximine
(analogs & derivatives, pharmacology)
- Rats
- Rats, Inbred F344
- Succinates
(toxicity)
- Succinimides
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