Metallomics Research
Online ISSN : 2436-5173
Publication Data
Regular article
  • Chihiro Tanaka, Yuki Naito, Yutaka Yoshikawa, Hiroyuki Yasui
    2023 年 3 巻 2 号 p. reg01-reg12
    発行日: 2023/06/20
    公開日: 2023/06/29
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    The increasing number of patients with diabetes has recently become a serious problem following changes in diet and lifestyle. Various drugs are used to treat diabetes; however, there are serious concerns regarding their physical and mental side effects. Zinc, copper, and nickel are trace elements present in the body that are known to have insulin-like effects although nickel is not essential to mammals. Here, we focused on metal complexes with the 2-acetylpyrazine N(4)-phenylthiosemicarbazone (2-APTC) ligand, which has a six-coordinate octahedral structure with an S2N4-type coordination mode. For single oral administration experiments, [Zn(2-APTC)2], zinc sulfate (10 mg Zn/kg) and [Cu(2-APTC)2], and copper sulfate (3 mg Cu/kg) were orally administered to 5-week-old ddy mice fasted for 12 h. Moreover, of [Zn(2-APTC)2] was administered daily to KK-Ay mice, a type 2 diabetes model. In a single oral administration experiment, [Zn(2-APTC)2] showed a significant increase in plasma zinc concentration compared to zinc sulfate. Moreover, the 28-d administration of [Zn(2-APTC)2] resulted in a significant decrease in the blood glucose level. This suggests that [Zn(2-APTC)2] has a higher absorption of the complexes than [Cu(2-APTC)2] after oral administration and is expected to have more antidiabetic activity. However, blood urea nitrogen, aspartate aminotransferase, and alanine transaminase levels increased, suggesting that [Zn(2-APTC)2] administration affects liver and kidney functions. Moreover, hematoxylin and eosin staining showed that [Zn(2-APTC)2] ameliorated fatty liver and exerted antidiabetic effects. Here, we report for the first time that a zinc complex with a six-coordinated octahedral structure, with 2-APTC as a ligand, exhibits antidiabetic effects.

  • Shinichi Katsumata, Hiroshi Matsuzaki
    2023 年 3 巻 2 号 p. reg13-reg20
    発行日: 2023/06/20
    公開日: 2023/06/29
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    Iron plays important roles in bone health as it is required as a cofactor for renal 25-hydroxyvitamin D-1α-hydroxylase, which is involved in the production of 1,25-dihydroxyvitamin D3 (active vitamin D), and regulates the expression of proteins involved bone formation. Herein, we investigated the effects of dietary iron supplementation on bone formation in iron-deficient rats. Male Wistar rats were fed a control (n = 12) or iron-deficient diet (n = 18) for 30 days, after which 6 rats in the iron-deficient group were switched to the control diet for 14 days. At the end of the 30-day period, hemoglobin, liver iron, serum 1,25-dihydroxyvitamin D3, and serum osteocalcin concentrations, and femoral bone mineral density (BMD) were found to be significantly lower in iron-deficient rats than that in control rats. Following dietary iron supplementation, hemoglobin and liver iron concentrations elevated significantly in iron-deficient rats; however, they were not restored to the normal levels. Additionally, dietary iron supplementation increased serum 1,25-dihydroxyvitamin D3 and osteocalcin concentrations and femoral mRNA expression of Bglap and Col1a1 in iron-deficient rats, which were downregulated by iron deficiency, to levels similar to that in control rats. However, femoral BMD was not recovered with dietary iron supplementation. These results suggest that iron deficiency-induced downregulation of bone formation can potentially be reversed by dietary iron supplementation. Furthermore, elevated serum 1,25-dihydroxyvitamin D3 concentrations due to dietary iron supplementation could be responsible for increased expression of bone formation markers in iron-deficient rats.

  • Yasunori Fukumoto, Dongyue Wang, Yu-ki Tanaka, Noriyuki Suzuki, Yasumi ...
    2023 年 3 巻 2 号 p. reg21-reg28
    発行日: 2023/06/26
    公開日: 2023/07/10
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    Methylmercury (MeHg) is a neurotoxic chemical of significant public health concern. Acute exposure to MeHg causes inhibition of cellular proliferation and DNA replication in cellular and animal models, and impedes S-phase entry and progression in several types of primary and cultured cells. However, the effect of MeHg on the DNA damage response remains unknown. The ATM and ATR pathways are two major components of the DNA damage response that regulate cell cycle progression. Here we report that acute MeHg exposure enhanced DNA replication stress in S phase. MeHg also inhibited the kinase activity of ATR, suggesting that replication forks collapsed in S phase. Moreover, MeHg promoted the degradation of Rad17 as a possible mechanism underlying the inactivation of ATR. These results suggest a novel connection between acute MeHg exposure and the ATR pathway, providing insight into a yet unidentified mechanism of the inactivation of Rad17 and the ATR pathway.

  • Atsuko Shinohara, Takehisa Matsukawa, Shinzo Kimura, Kazuhito Yokoyama ...
    2023 年 3 巻 2 号 p. reg29-reg41
    発行日: 2023/08/28
    公開日: 2023/09/13
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    Concentrations of 40 kinds of elements in water samples collected around Chornobyl nuclear power plant (CNPP) in September 2017 were determined using ICP-MS to investigate possible adverse effects on residents’ health. Regional characteristics of elements of Chornobyl and Narodychi district, which suffered high radioactivity due to the accident on 1986, were compared with those of other cities in Ukraine, Belarus, and Japan. The concentrations of toxic elements such as As, Cd, Pb, and Se in Chornobyl and Narodychi were lower than regulation values of WHO guidelines for drinking-water quality, and not particularly higher than those of other cities. Among three well water samples of Chornobyl, one or two contained much higher concentrations of Mn, Zn or La than tap water or hand washing water. Three well water and one tap water samples of Chornobyl were also collected in April 2018, August 2019, and January 2020 in order to know the yearly change of elements. Changes in concentrations of alkali and alkaline earth elements were relatively small, and those of transition elements were large. Pb concentrations of most of samples were lower than 0.3 μg/L, but an extremely high value of 340 μg/L was observed temporarily in one well water sample in 2019, although the source of Pb was not clear. These results did not suggest notable health problems associated with elements in the water of Chornobyl.

  • Shinichi Katsumata, Hiroshi Matsuzaki
    2023 年 3 巻 2 号 p. note01-note07
    発行日: 2023/07/20
    公開日: 2023/07/31
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    To determine the underlying mechanism of iron deficiency-induced bone loss, we investigated the effects of dietary iron deficiency on bone metabolism-related mRNA expression in rats. Weanling male Wistar rats were divided into three groups, each comprising six rats. Rats in two of the three groups were given free access to either a control (C group) or an iron-deficient (D group) diet for 4 weeks. Rats in the PF group were pair-fed the control diet with rats in the D group. Hemoglobin concentration, serum osteocalcin concentration, femoral bone mineral content and density, and femoral Igf1, Bmp2, Runx2, Sp7, Spp1, Bglap, and Col1a1 mRNA expression were significantly lower in the D group than in the C and PF groups. Additionally, urinary deoxypyridinoline excretion and femoral Acp5 mRNA expression were significantly lower in the D group than in the C and PF groups. These results suggested that dietary iron deficiency reduced osteoblastogenesis by decreasing the expression of insulin-like growth factor-1 and bone morphogenetic protein 2. Furthermore, bone resorption parameters indicated a decrease in bone resorption in iron-deficient rats.