Davis M E
Department of Pharmacology and Toxicology, West Virginia University, Morgantown 26506.
Toxicol Appl Pharmacol. 1988 Aug;95(1):44-52. doi: 10.1016/s0041-008x(88)80006-1.
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.
利用经AT - 125（阿西维辛；L-(αS, 5S)-α-氨基-3-氯-4,5-二氢-5-异恶唑乙酸）预处理的雄性斯普拉格-道利大鼠，研究了γ-谷氨酰转肽酶（γ-GTP）在六氯-1,3-丁二烯（HCBD）肾毒性中的作用。γ-GTP活性被抑制超过95%对尿量、肾小球滤过率或滤液、钠或葡萄糖的肾小管重吸收没有影响。在HCBD给药后的最初24小时内观察到的肾毒性，并不会因γ-GTP的抑制而降低，并且在24小时之后，经AT - 125预处理的组中肾毒性增加而非降低。HCBD会损害葡萄糖重吸收，而这在经AT - 125预处理的组中显著增加，表明肾单位起始段的功能受到了HCBD的损害。由于γ-GTP的抑制并不能预防HCBD的肾毒性，因此得出结论，γ-GTP抑制并不会限制导致HCBD肾毒性的代谢物的形成。所以，γ-谷氨酰转肽酶的分布并不能解释六氯-1,3-丁二烯的选择性肾毒性。
