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大鼠长期口服氯化镉和镉-金属硫蛋白后的肾毒性比较。

Comparison of renal toxicity after long-term oral administration of cadmium chloride and cadmium-metallothionein in rats.

作者信息

Groten J P, Koeman J H, van Nesselrooij J H, Luten J B, Fentener van Vlissingen J M, Stenhuis W S, van Bladeren P J

机构信息

Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.

出版信息

Fundam Appl Toxicol. 1994 Nov;23(4):544-52. doi: 10.1006/faat.1994.1139.

Abstract

There is a clear lack of information on the toxicological risk of dietary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose-dependent cadmium (Cd) disposition and to investigate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl2) in rats. Male Wistar rats were fed diets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl2 for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl2 the Cd concentrations in intestine, liver, and kidneys were all higher than in rats fed the same doses in the form of CdMt. The kidney/liver Cd concentration ratio was higher with CdMt than with CdCl2. At the lower Cd concentrations (0.3 and 3 mg/kg), no differences in Cd accumulation between CdMt and CdCl2 groups were observed and the kidney/liver Cd ratio was also similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl2 had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indicated by an increase of urinary lactate dehydrogenase (LDH) activity, were seen 4 months after exposure to 90 mg/kg Cd as CdCl2. After 8 and 10 months the renal effect of 90 mg/kg Cd as CdCl2 became more pronounced and urinary enzyme activities of LDH, N-acetyl-beta-D-glucosaminidase and alkaline phosphatase were all elevated. The only clinical effect of CdMt at the dose level of 90 mg/kg was a slight increase in urinary gamma-glutamyl transpeptidase activity at 8 and 10 months.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

关于饮食摄入镉 - 金属硫蛋白(CdMt)的毒理学风险,目前明显缺乏相关信息。本研究旨在确定镉(Cd)的剂量依赖性处置情况,并调查大鼠长期经饮食接触CdMt或氯化镉(CdCl2)后肾毒性的差异。将雄性Wistar大鼠分别喂食含0.3、3、30或90 mg Cd/kg的CdMt或CdCl2饮食,持续10个月。在喂食30和90 mg/kg CdCl2的大鼠中,肠道、肝脏和肾脏中的Cd浓度均高于喂食相同剂量CdMt的大鼠。CdMt组的肾/肝Cd浓度比高于CdCl2组。在较低的Cd浓度(0.3和3 mg/kg)下,未观察到CdMt组和CdCl2组之间Cd积累的差异,肾/肝Cd比值也相似。当基于组织中每毫克Cd的CdMt量计算时,喂食CdMt的大鼠和喂食CdCl2的大鼠在肝脏和肾脏中的相对CdMt浓度相似。以尿乳酸脱氢酶(LDH)活性增加为指标的肾损伤最初迹象,在接触90 mg/kg CdCl2 4个月后出现。8个月和10个月后,90 mg/kg CdCl2的肾效应变得更加明显,尿中LDH、N - 乙酰 - β - D - 氨基葡萄糖苷酶和碱性磷酸酶的酶活性均升高。90 mg/kg剂量水平的CdMt的唯一临床效应是在8个月和10个月时尿γ - 谷氨酰转肽酶活性略有增加。(摘要截断于250字)

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