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低剂量氯化汞对F344大鼠和多乳鼠(南非多乳鼠)的比较生化效应

Comparative biochemical effects of low doses of mercury II chloride in the F344 rat and the multimammate mouse (Mastomys natalensis).

作者信息

Holmes E, Bonner F W, Nicholson J K

机构信息

Department of Chemistry, Birkbeck College, London, UK.

出版信息

Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1996 May;114(1):7-15. doi: 10.1016/0742-8413(95)02105-1.

Abstract

The biochemical effects and comparative nephroxicity of mercury II chloride (HgCl2) dosed at 0.75 mg/kg i.p. was investigated in the Fisher 344 rat (F344) and Mastomys natalensis using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy of urine, histopathology and clinical chemical techniques. The effects of HgCl2 treatment were followed for up to 4 days post-dosing (p.d.). In F344 rats there was extensive proximal tubular damage and renal cortical necrosis together with elevated levels of urinary gamma-glutamyl transpeptidase (gamma GT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The 1H NMR spectra of urine obtained from Hg-treated F344 rats also showed increased levels of glucose, alanine, lactate, valine and hippurate (0-48h p.d.) with decreased levels of citrate, succinate and 2-oxoglutarate (24-48h p.d.). Mastomys were found to be highly resistant to HgCl2 toxicity at 0.75 mg/kg and the histological appearance of the renal cortex of treated animals was virtually identical to controls. There were no elevations in urinary ALP, gamma GT and LDH activities in HgCl2-treated Mastomys and there were no biochemical abnormalities in low MW components of Mastomys urine following HgCl2-treatment, as shown by 1H NMR spectroscopy. Urinary gamma GT activity was found to be much higher in F344 rats than Mastomys. Since gamma GT activity is involved in the tubular reabsorption of Hg2+, the lower levels of gamma GT in Mastomys might partially account for the lower toxicity of Hg2+ in this species.

摘要

采用尿液的高分辨率氢核磁共振(NMR)光谱、组织病理学和临床化学技术,研究了腹腔注射剂量为0.75mg/kg的氯化汞(HgCl₂)对费希尔344大鼠(F344)和南非乳鼠的生化效应及比较肾毒性。给药后长达4天(p.d.)跟踪HgCl₂处理的效果。在F344大鼠中,出现了广泛的近端肾小管损伤和肾皮质坏死,同时尿γ-谷氨酰转肽酶(γGT)、碱性磷酸酶(ALP)和乳酸脱氢酶(LDH)水平升高。从经Hg处理的F344大鼠获得的尿液的¹H NMR光谱还显示,葡萄糖、丙氨酸、乳酸、缬氨酸和马尿酸盐水平升高(给药后0 - 48小时),而柠檬酸盐、琥珀酸盐和2-氧代戊二酸水平降低(给药后24 - 48小时)。发现南非乳鼠对0.75mg/kg的HgCl₂毒性具有高度抗性,处理动物的肾皮质组织学外观与对照几乎相同。HgCl₂处理的南非乳鼠的尿ALP、γGT和LDH活性没有升高,¹H NMR光谱显示,HgCl₂处理后南非乳鼠尿液的低分子量成分没有生化异常。发现F344大鼠的尿γGT活性比南非乳鼠高得多。由于γGT活性参与Hg²⁺的肾小管重吸收,南非乳鼠中较低水平的γGT可能部分解释了该物种中Hg²⁺较低的毒性。

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