Sex differences in shotgun proteome analyses for chronic oral intake of cadmium in mice

• Published in: PloS one Vol. 10; no. 3; p. e0121819
• Main Authors: Yamanobe, Yoshiharu, Nagahara, Noriyuki, Matsukawa, Takehisa, Ito, Takaaki, Niimori-Kita, Kanako, Chiba, Momoko, Yokoyama, Kazuhito, Takizawa, Toshihiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2015; Public Library of Science (PLoS)
• Subjects: Accumulation; Administration, Oral; Analysis; Animals; Biocompatibility; Biomedical materials; Cadmium; Cadmium - metabolism; Chemicals; Cytotoxicity; Disease; Down-Regulation; Drinking water; Drug dosages; Environmental diseases; Environmental health; Epidemiology; Experiments; Exposure; Female; Females; Food contamination; Gender aspects; Gender differences; Glutathione; Glutathione transferase; Inductively coupled plasma; Inductively coupled plasma mass spectrometry; Industrial pollution; Industrial wastes; Industrial wastewater; Kidney - metabolism; Kidney - pathology; Kidneys; Laboratory animals; Liver; Liver - metabolism; Liver - pathology; Male; Males; Mass spectrometry; Mass spectroscopy; Medical schools; Medicine; Metals; Mice; Mice, Inbred C57BL; Oral administration; Osteomalacia; Outbreaks; Poisoning; Proteome - metabolism; Proteomes; Proteomics; Proteomics - methods; Reference materials; Renal function; River basins; Rivers; Rodents; Sex Characteristics; Sex differences; Studies; Thyroid; Thyroid gland; Up-Regulation; Wastewater; Wastewater pollution; Water analysis; Water pollution; Water-borne diseases; Waterborne diseases; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0121819

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.