Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Volume 5, Issue 3
Displaying 1-5 of 5 articles from this issue
  • Jin-Yong Lee, Maki Tokumoto, Gi-Wook Hwang, Masahiko Satoh
    2018 Volume 5 Issue 3 Pages 93-97
    Published: May 30, 2018
    Released on J-STAGE: May 30, 2018

    Cadmium (Cd) is an environmental pollutant which triggers toxic effects on various tissues, including the kidney. Proximal tubular cell damage is characteristic of Cd-induced renal toxicity. In our previous study, DNA microarray results showed that Cd treatment changed the expression levels of many genes in HK-2 human proximal tubular cells. Among the genes which increased their expression levels after Cd treatment, there were several genes coding for heat shock proteins. In the current study, we examined the role of heat shock protein genes in Cd-induced toxicity in HK-2 cells. Cd treatment increased the expression of the HSPA1, HSPH1, and HSPA8 genes in HK-2 cells. From these identified genes, only knockdown of HSPH1 and HSPA8 by siRNA treatment was found to decrease the viability of low-dose Cd-treated HK-2 cells compared with the control siRNA treatment group. These results suggest that several heat shock proteins are involved in the pathway which protects HK-2 cells against Cd toxicity.

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Original Article
  • Tomoko Inubushi, Mayumi Sugimoto, Haruka Kunimi, Haruka Hino, Atsushi ...
    2018 Volume 5 Issue 3 Pages 99-103
    Published: June 01, 2018
    Released on J-STAGE: June 01, 2018

    Biphenyl is a universal intermediate agent used as a protectant in various industrial activities. Biphenyl is currently used in postharvest applications as a fungicide in foreign countries to maintain the safety and quality of agricultural products. However, the risk of using biphenyl is in dispute in Japan. The toxicity of biphenyl has been studied in animals, and reportedly affects the liver and kidney especially. However, the toxic effect of biphenyl on cells is currently not well-understood, and the mechanism is unclear. We examined the toxicity of biphenyl on HL60 cells, a human promyelocytic leukemia cell line, by performing flow cytometry analyses with fluorescent probes. Biphenyl at 100 μM or greater significantly increased lethality and the intensity of side scatter on HL60 cells. Moreover, biphenyl at 30 μM or greater increased intracellular Ca2+ in a concentration-dependent manner. This increase resulted from free extracellular Ca2+ entering into the cells. These results indicate that an increase in intracellular Ca2+ may be one of several causes of the cytotoxicity induced by biphenyl. This study will contribute to the safety evaluation of biphenyl in the future.

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Original Article
  • Shiori Fukaya, Akito Nagatsu, Hiroki Yoshioka
    2018 Volume 5 Issue 3 Pages 105-112
    Published: June 19, 2018
    Released on J-STAGE: June 19, 2018

    The aim of this study was to investigate whether the Japanese herbal medicine “Juzen-taiho-to (JTX)” has a protective effect on ethanol (EtOH)-induced liver injury. Seven-week-old male ICR mice were orally administered JTX or saline once a day for three days. Twenty-four hours after the last administration, the mice were intraperitoneally injected with EtOH (2 g/kg). The mice in each group were killed 24 hr after EtOH administration and were bled to obtain plasma. The mice injected with EtOH had high plasma levels of alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. Histopathological examination of the liver of mice treated with EtOH revealed an abnormal outline around the central vein, glycogen depletion, and expression of prostaglandin-endoperoxide synthase 2. Pretreatment with JTX prevented the EtOH-induced increase in the levels of alanine aminotransferase and aspartate aminotransferase, lipid peroxidation, and histopathological changes. Our results suggest that JTX exerts protective effects against EtOH-induced liver disease by modulating oxidative stress and inflammatory response.

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  • Atsuko Miyajima, Yukie Kuroda, Kazue Sakemi-Hoshikawa, Makoto Usami, K ...
    2018 Volume 5 Issue 3 Pages 113-116
    Published: June 19, 2018
    Released on J-STAGE: June 19, 2018

    The metabolism of 4-methyl-2-mercaptobenzimidazole (4-MeMBI), 5-methyl-2-mercaptobenzimidazole (5-MeMBI), and 2-mercaptobenzimidazole (MBI) was examined in vitro in rat liver microsomes. The test chemicals were incubated in the presence of liver microsomes from male Sprague-Dawley rats, and their metabolism was analyzed by HPLC. The metabolism amount increased in an incubation time-dependent manner, and was similar among the test chemicals. SKF-525A, a non-selective inhibitor of cytochrome P450 (CYP) enzymes, decreased the metabolic rate of all the test chemicals, indicating the involvement of liver microsomal CYP enzymes. When liver microsomes from rats treated with CYP-inducers (β-naphthoflavone, phenobarbital, and isoniazid) were used, 4-MeMBI was more decreased than 5-MeMBI, particularly in the phenobarbital-treated group. These results, together with the reported inducibility of the drug-metabolizing activity by the test chemicals, partly explained the counteraction in the toxic effects between 4-MeMBI and 5-MeMBI in the in vivo study.

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  • Isao Maruyama, Takuya Uchikawa, Toshihiro Kanno, Yotaro Ando, Hisao Ki ...
    2018 Volume 5 Issue 3 Pages 117-122
    Published: June 21, 2018
    Released on J-STAGE: June 21, 2018

    An open-label clinical trial was performed to test the effects of unicellular green alga Chlorella supplementation on mercury concentrations of hair and blood in healthy subjects. Fifty-eight healthy participants (36 male and 22 female) were assigned to Chlorella and control groups. The Chlorella group of 35 subjects received Chlorella tablets (9 g/day) for an experimental period of 3 months while the control group of 23 subjects did not. Total mercury concentrations of hair and blood were analyzed at the beginning and end of the experimental period for estimation of methylmercury (MeHg) levels in the body. The hair mercury concentration of the Chlorella group (n = 33) was significantly decreased during the experimental period (p = 0.041) while the change in the control group (n = 23) was not significant (p = 0.362). Although the decrease in blood mercury concentration in the Chlorella group (n = 19) was not significant (p = 0.084), the change of values (values at end – values at beginning) in this group was significantly greater than that in the control group (n = 20, p = 0.038). The fish intake rates remained relatively constant during the experimental period in both the Chlorella and control groups. These results suggest that supplementation with Chlorella for 3 months in healthy subjects might reduce their body MeHg levels.

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