Yamanobe Yoshiharu, Nagahara Noriyuki, Matsukawa Takehisa, Ito Takaaki, Niimori-Kita Kanako, Chiba Momoko, Yokoyama Kazuhito, Takizawa Toshihiro
Isotope Research Center, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
Department of Epidemiology and Environmental Health, Juntendo University, Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
PLoS One. 2015 Mar 20;10(3):e0121819. doi: 10.1371/journal.pone.0121819. eCollection 2015.
Environmental diseases related to cadmium exposure primarily develop owing to industrial wastewater pollution and/or contaminated food. In regions with high cadmium exposure in Japan, cadmium accumulation occurs primarily in the kidneys of individuals who are exposed to the metal. In contrast, in the itai-itai disease outbreak that occurred in the Jinzu River basin in Toyama Prefecture in Japan, cadmium primarily accumulated in the liver. On the other hand, high concentration of cadmium caused renal tubular disorder and osteomalacia (multiple bone fracture), probably resulting from the renal tubular dysfunction and additional pathology. In this study, we aimed to establish a mouse model of chronic cadmium intake. We administered cadmium-containing drinking water (32 mg/l) to female and male mice ad libitum for 11 weeks. Metal analysis using inductively coupled plasma mass spectrometry revealed that cadmium accumulated in the kidneys (927 x 10 + 185 ng/g in females and 661 x 10 + 101 ng/g in males), liver (397 x 10 + 199 ng/g in females and 238 x 10 + 652 ng/g in males), and thyroid gland (293 + 93.7 ng/g in females and 129 + 72.7 ng/g in males) of mice. Female mice showed higher cadmium accumulation in the kidney, liver, and thyroid gland than males did (p = 0.00345, p = 0.00213, and p = 0.0331, respectively). Shotgun proteome analyses after chronic oral administration of cadmium revealed that protein levels of glutathione S-transferase Mu2, Mu4, and Mu7 decreased in the liver, and those of A1 and A2 decreased in the kidneys in both female and male mice.
与镉暴露相关的环境疾病主要是由于工业废水污染和/或受污染的食物而产生的。在日本镉暴露水平较高的地区，镉主要在接触该金属的个体的肾脏中蓄积。相比之下，在日本富山县神通川流域发生的痛痛病疫情中，镉主要蓄积在肝脏中。另一方面，高浓度的镉会导致肾小管紊乱和骨软化症（多发性骨折），这可能是由肾小管功能障碍及其他病理情况引起的。在本研究中，我们旨在建立一个慢性镉摄入的小鼠模型。我们随意给雌性和雄性小鼠饮用含镉的饮用水（32毫克/升），持续11周。使用电感耦合等离子体质谱法进行的金属分析表明，镉蓄积在小鼠的肾脏（雌性为927×10 + 185纳克/克，雄性为661×10 + 101纳克/克）、肝脏（雌性为397×10 + 199纳克/克，雄性为238×10 + 652纳克/克）和甲状腺（雌性为293 + 93.7纳克/克，雄性为129 + 72.7纳克/克）中。雌性小鼠在肾脏、肝脏和甲状腺中的镉蓄积量高于雄性小鼠（分别为p = 0.00345、p = 0.00213和p = 0.0331）。慢性口服镉后进行的鸟枪法蛋白质组分析表明，雌性和雄性小鼠肝脏中的谷胱甘肽S -转移酶Mu2、Mu4和Mu7的蛋白质水平均下降，而肾脏中的A1和A2的蛋白质水平下降。
