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Effects of AT-125 on the nephrotoxicity of hexachloro-1,3-butadiene in rats.

Abstract：

:The role of gamma-glutamyl transpeptidase (gamma-GTP) in the nephrotoxicity of hexachloro-1,3-butadiene (HCBD) was studied using male Sprague-Dawley rats pretreated with AT-125 (Acivicin; L-(alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid). Inhibition of gamma-GTP by more than 95% did not affect urine output, glomerular filtration rate, or tubular reabsorption of filtrate, sodium, or glucose. Nephrotoxicity observed during the first 24 hr after HCBD was not decreased by inhibition of gamma-GTP and beyond 24 hr nephrotoxicity was increased, rather than decreased, in the AT-125-pretreated group. HCBD impairs glucose reabsorption and this was greatly increased in the AT-125-pretreated group, indicating that function of the initial segment of the nephron is impaired by HCBD. Since inhibition of gamma-GTP did not protect against HCBD nephrotoxicity, it is concluded that gamma-GTP inhibition does not limit the formation of metabolites(s) which cause HCBD nephrotoxicity. Therefore, distribution of gamma-glutamyltranspeptidase does not account for the selective nephrotoxicity of hexachloro-1,3-butadiene.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Davis ME

doi

10.1016/s0041-008x(88)80006-1

subject

Has Abstract

pub_date

1988-08-01 00:00:00

pages

44-52

issue

1

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(88)80006-1

journal_volume

95

pub_type

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