Nephrotoxic potential of N-(3,5-dichlorophenyl)glutarimide and N-(3,5-dichlorophenyl)glutaramic acid in Fischer 344 rats.
The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) produces kidney damage in rats. Although many NDPS analogues have been screened as possible nephrotoxicants, the one-carbon homologue, N-(3,5-dichlorophenyl)glutarimide (NDPG), has not been evaluated. This study examined the nephrotoxic potential of NDPG and a putative metabolite, N-(3,5-dichlorophenyl)glutaramic acid (NDPGA). Male Fischer 344 rats (N = 3-4 per group) were administered a single i.p. injection in corn oil of NDPG or NDPGA (0.4 or 1.0 mmol/kg), NDPS (0.4 mmol/kg), or corn oil alone. Renal function was monitored for 48 h. In contrast to NDPS, NDPG and NDPGA did not significantly alter renal function or kidney morphology when compared to corn oil-treated controls. These experiments show that replacement of the succinimide ring in NDPS with a glutarimide ring abolishes toxicity.
D000818:Animals; D001806:Blood Urea Nitrogen; D002722:Chlorobenzenes / Q000737:chemistry / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005659:Fungicides, Industrial / Q000737:chemistry / Q000633:toxicity*; D005977:Glutarates / Q000737:chemistry / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010881:Piperidones / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000737:chemistry / Q000633:toxicity
D002722:Chlorobenzenes; D005659:Fungicides, Industrial; D005977:Glutarates; C096664:N-(3,5-dichlorophenyl)glutaramic acid; D010881:Piperidones; D013388:Succinimides; C007352:N-(3,5-dichlorophenyl)succinimide; C096665:N-(3,5-dichlorophenyl)glutarimide