Effect of buthionine sulfoximine on acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in Fischer 344 rats.
The experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) has been shown to be a nephrotoxicant in Fischer 344 rats. Results of a previous study conducted in our laboratory suggested that glutathione might be an important modulator of NDPS-induced nephrotoxicity. The purpose of this study was to examine the effect of DL-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, on NDPS-induced renal effects. Male Fischer 344 rats received an intraperitoneal (i.p.) injection of BSO (890 mg/kg) in 0.9% saline (10 ml/kg) followed 2 h later by an i.p. injection of NDPS (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg), and renal function monitored at 24 and 48 h. BSO pretreatment attenuated the diuresis, proteinuria, elevation in blood urea nitrogen (BUN) concentration and kidney weight, and decreases in organic ion accumulation by renal cortical slices induced by NDPS (0.4 or 1.0 mmol/kg) administration. Proximal tubular necrosis induced by NDPS administration also was attenuated by BSO pretreatment. These results indicate that BSO pretreatment attenuates NDPS-induced renal effects and that glutathione is important for modulating acute NDPS-induced nephropathy.
Rankin
G O
GO
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Teets
V J
VJ
Nicoll
D W
DW
Brown
P I
PI
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D005978:Glutathione / Q000096:biosynthesis; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013388:Succinimides / Q000633:toxicity*; D013997:Time Factors
D000963:Antimetabolites; D013388:Succinimides; D008717:Methionine Sulfoximine; C007352:N-(3,5-dichlorophenyl)succinimide; D019328:Buthionine Sulfoximine; D005978:Glutathione