Ohta H, Yamauchi Y, Nakakita M, Tanaka H, Asami S, Seki Y, Yoshikawa H
Department of Occupational Health and Toxicology, School of Allied Health Sciences, Kitasato University, Kanagawa, Japan.
Ind Health. 2000 Oct;38(4):339-55. doi: 10.2486/indhealth.38.339.
To investigate the importance of the cadmium (Cd) exposure condition in the evaluation of toxic effect on renal function and bone metabolism, six groups of Male Wistar rats were given Cd at respective daily doses of 2, 5, 10, 20, 30 and 60 mgCd/kg (as CdCl2) via a gastric tube for 6 consecutive days a week for 60 weeks. In the groups given a low Cd dose (2, 5 and 10 mgCd/kg), relatively more Cd accumulated in the kidney without liver damage than in the liver. In the high Cd dose groups (20, 30 and 60 mgCd/kg), on the other hand, more Cd accumulated in the liver than in the kidney. The daily intake of Cd dose from the intestinal tract in each experimental group was deduced to be about 0.36%-0.54% of the cumulative dose of oral Cd administration. The daily intake of Cd into the body was estimated as 7, 22, 40, 100, 120, 260 microgCd/kg/day in the experimental groups of 2, 5, 10, 20, 30 and 60 mgCd/kg/day, respectively. Increase of plasma enzyme activity (GOT, GPT) and of urinary enzyme excretion (NAG, AAP, GST), reflecting hepatic damage and renal dysfunction, was found in the high Cd dose groups (30 and 60 mgCd/kg) from the 5th week. Non-CdMT concentration in the kidney was also significantly high in the high Cd dose groups. In the low Cd dose groups (2 and 5 mgCd/kg), although the renal Cd concentration was higher than that of the high Cd dose groups, prominent renal dysfunction and hepatic damage were not observed. Regeneration, vacuolization, and eosinophilic bodies in proximal tubular tissue were mainly observed in the groups subjected to 20, 30 and 60 mgCd/kg administration. Very slight regeneration was also observed in the renal proximal tubular tissue at the 30th week for the 5 mgCd/kg and 10 mgCd/kg groups, and at the 60th week for the 2 mgCd/kg group. Remarkable decrease of bone mineral density at the midpoint of the femur was found in the high Cd dose groups. Also, the decrease in bone mineral density was observed before or after the manifestation of the renal dysfunction, depending on the dose and the duration of Cd administration. Urinary excretion of Pyr, DPyr, and Ca increased and plasma BGP decreased in the higher Cd dose groups. Osteoid volume in the femur tissue was not increased significantly by Cd exposure. Based on these results, it was suggested that Cd exposure caused osteoporotic change. The results of the present study suggested that the toxic effect of Cd on renal function and that on bone metabolism were caused at different times and that renal Cd concentration after long-term oral Cd administration depended on the dose and the duration of Cd exposure.
为研究镉（Cd）暴露条件在评估其对肾功能和骨代谢毒性作用中的重要性，将六组雄性Wistar大鼠通过胃管分别给予每日剂量为2、5、10、20、30和60 mgCd/kg（以CdCl₂形式）的镉，每周连续6天，共60周。在低镉剂量组（2、5和10 mgCd/kg）中，相较于肝脏，肾脏中积累的镉相对较多，且无肝脏损伤。另一方面，在高镉剂量组（20、30和60 mgCd/kg）中，肝脏中积累的镉比肾脏中多。各实验组经肠道每日摄入的镉剂量约为口服镉累积剂量的0.36%-0.54%。各实验组经口摄入体内的镉量估计分别为7、22、40、100、120、260 μgCd/kg/天，对应剂量分别为2、5、10、20、30和60 mgCd/kg/天。从第5周起，在高镉剂量组（30和60 mgCd/kg）中发现反映肝损伤和肾功能不全的血浆酶活性（GOT、GPT）及尿酶排泄（NAG、AAP、GST）增加。高镉剂量组肾脏中非镉金属硫蛋白（CdMT）浓度也显著升高。在低镉剂量组（2和5 mgCd/kg）中，尽管肾脏镉浓度高于高镉剂量组，但未观察到明显的肾功能不全和肝损伤。在给予20、30和60 mgCd/kg镉的组中，主要观察到近端肾小管组织的再生、空泡化和嗜酸性小体。在第30周时，5 mgCd/kg和10 mgCd/kg组以及在第60周时，2 mgCd/kg组的肾近端肾小管组织也观察到非常轻微的再生。高镉剂量组股骨中点骨密度显著降低。此外，根据镉给药剂量和持续时间的不同，在肾功能不全表现之前或之后观察到骨密度降低。高镉剂量组尿中吡啶啉（Pyr）、脱氧吡啶啉（DPyr）和钙的排泄增加，血浆骨钙素（BGP）降低。镉暴露未使股骨组织类骨质体积显著增加。基于这些结果表明，镉暴露导致骨质疏松性改变。本研究结果表明，镉对肾功能和骨代谢的毒性作用在不同时间产生，长期口服镉后肾脏镉浓度取决于镉暴露的剂量和持续时间。
