Suzuki C A, Cherian M G
Department of Pharmacology, University of Western Ontario, London, Canada.
J Biochem Toxicol. 1988 Spring;3:11-20. doi: 10.1002/jbt.2570030103.
The effects of cadmium-metallothionein (Cd-MT) on organic ion uptake in renal cortical slices and lipid peroxidation in the kidney were studied in rats. For in vitro studies, slices were prepared from kidneys of control animals and incubated in buffer containing either cadmium chloride (CdCl2) or Cd-MT in equimolar Cd concentrations ranging from 5 x 10(-6) to 2 x 10(-4) M. Uptake into the slices of the organic anion p-aminohippuric acid (PAH) was found to be inhibited by both forms of Cd in a dose-dependent manner. Although this inhibition was slightly greater in the presence of Cd-MT, accumulation of Cd into the slices was approximately 12 times greater with CdCl2 than Cd-MT. Tetraethylammonium (TEA) uptake was less sensitive to the inhibitory effects of both CdCl2 and Cd-MT, although a dose-dependent inhibition did occur with higher Cd concentrations. To study the in vivo effects of Cd-MT on transport function and lipid peroxidation in the kidney, rats were injected with Cd-MT (0.3 mg Cd per kilogram body weight [bw]) and sacrificed at specific time intervals. Similar to the in vitro studies, PAH uptake into the renal cortical slices was markedly inhibited within 12 hours after Cd-MT injection whereas inhibition of TEA uptake was less and not observed until 48 hours after injection. Only a small increase (1.4-fold) in lipid peroxidation, as measured by generation of malondialdehyde (MDA), in the kidney was detected at four hours postinjection, and no further increase was observed at later time periods. The results suggest that Cd-MT affects the transport of organic anions and cations during its renal uptake but that lipid peroxidation may play only a minor role in Cd-MT-induced renal toxicity.
研究了镉-金属硫蛋白（Cd-MT）对大鼠肾皮质切片中有机离子摄取及肾脏脂质过氧化的影响。在体外研究中，从对照动物的肾脏制备切片，并在含有氯化镉（CdCl₂）或Cd-MT的缓冲液中孵育，Cd浓度等摩尔，范围为5×10⁻⁶至2×10⁻⁴M。发现有机阴离子对氨基马尿酸（PAH）进入切片的摄取受到两种形式镉的剂量依赖性抑制。虽然在Cd-MT存在下这种抑制作用略强，但CdCl₂使镉在切片中的蓄积量比Cd-MT大约12倍。四乙铵（TEA）摄取对CdCl₂和Cd-MT的抑制作用不太敏感，尽管在较高镉浓度下确实出现了剂量依赖性抑制。为了研究Cd-MT对肾脏转运功能和脂质过氧化的体内影响，给大鼠注射Cd-MT（每千克体重0.3mg镉[bw]），并在特定时间间隔处死。与体外研究相似，注射Cd-MT后12小时内，肾皮质切片对PAH的摄取明显受到抑制，而对TEA摄取的抑制作用较小，直到注射后48小时才观察到。注射后4小时，仅检测到肾脏中脂质过氧化有小幅增加（1.4倍），以丙二醛（MDA）生成量衡量，后期未观察到进一步增加。结果表明，Cd-MT在肾脏摄取过程中影响有机阴离子和阳离子的转运，但脂质过氧化在Cd-MT诱导的肾毒性中可能仅起次要作用。
