Organogermanium Compound, Ge-132, Forms Complexes with Adrenaline, Atp and Other Physiological
            <i>Cis</i>
            -Diol Compounds

Nakamura, Takashi; Shimada, Yasuhiro; Takeda, Tomoya; Sato, Katsuyuki; Akiba, Mitsuo; Fukaya, Haruhiko

doi:10.4155/fmc.15.62

Cited by 24 publications

(28 citation statements)

References 44 publications

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“…Compared with the FTIR data on repagermanium previously reported by Nakamura et al . 14 , the unique strong absorption wavelengths at 1686 cm −1 (peak 3) and 797 cm −1 (peak 5) originated from C = O and Ge-O-Ge in the Asai manufacturing repagermanium (Fig. 1A,C), and similar peaks were also observed in commercial repagermanium (Fig.…”

Section: Results and Disccusionsupporting

confidence: 57%

“…Repagermanium has also been reported to alleviate cancer pain and reduce the use of morphine as a pain killer 11,12 . In addition, THGP, a hydrolytic monomer of repagermanium, has been reported to interact with some biological cis-diol compounds, such as adrenaline, ATP and nucleic acids 14,15 , and repagermanium exerts a curative effect on burn injuries 16 . Terminal cancer and burn injuries cause pain through the leakage of ATP from necrotic cells, and THGP might therefore be beneficial for pain control in patients with these diseases.…”

Section: Introductionmentioning

confidence: 99%

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Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts

Takeda

Doiyama

Azumi

et al. 2019

Sci Rep

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Reactive oxygen species (ROS) are very harmful to dermal cells, and it is thus important to develop cosmetics that protect the skin from ROS and other stimuli. Repagermanium is a synthetic water-soluble organogermanium polymer, and in this study, we attempted to visualize the incorporation of germanium into normal human dermal fibroblasts (NHDFs) using isotope microscopy. In addition, the content of 3-(trihydroxygermyl)propanoic acid (THGP), a hydrolyzed monomer of repagermanium, in NHDFs was determined through liquid chromatography mass spectrometry (LC-MS/MS), and the dose-dependent incorporation of THGP was confirmed. We then evaluated the preventive effects of THGP against ROS-induced NHDF death and confirmed the observed preventive effects through gene profiling and expression analysis. The addition of 0.59–5.9 mM THGP reduced cell death resulting from ROS damage caused by the reaction between xanthine oxidase and hypoxanthine and the direct addition of H2O2. Furthermore, this study provides the first demonstration that the effect of THGP was not due to the direct scavenging of ROS, which indicates that the mechanism of THGP differs from that of general antioxidants, such as ascorbic acid. The gene profiling and expression analysis showed that THGP suppressed the expression of the nuclear receptor subfamily 4 group A member 2 (NR4A2) gene, which is related to cell death, and the interleukin 6 (IL6) and chemokine (C-X-C motif) ligand 2 (CXCL2) genes, which are related to the inflammatory response. Furthermore, the production of IL6 induced by H2O2 was suppressed by the THGP treatment. Our data suggest that the preventive effect of THGP against ROS-induced cell death is not due to antioxidant enzymes or ROS scavenging.

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Section: Results and Disccusionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts

Takeda

Doiyama

Azumi

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

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“…The results support that Ge-132 treatment may reduce excessive apoptosis or necrosis, which may result in impaired cellular growth and embryo fragments in accordance with cleavage pattern data in this study. Although very little is known regarding the mechanism of Ge-132 related to apoptosis, according to a recent study, Ge-132 can interact with physiological cis -diol compounds, such as adenosine triphosphate (ATP), and form complexes [ 49 ]. Intracellular ATP levels appear to be a factor that determines cell death fate by apoptosis and necrosis [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Carboxyethylgermanium sesquioxide (Ge-132) treatment during <i>in vitro</i> culture protects fertilized porcine embryos against oxidative stress induced apoptosis

Kim

Hwang

Yoon

et al. 2017

Journal of Reproduction and Development

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Compared with the in vivo environment, porcine in vitro embryo-culture systems are suboptimal, as they induce oxidative stress via the accumulation of reactive oxygen species (ROS). High ROS levels during early embryonic development cause negative effects, such as apoptosis. In this study, we examined the effects of the antioxidant carboxyethylgermanium sesquioxide (Ge-132) during in vitro culture (IVC) on embryonic development in porcine in vitro fertilization (IVF) embryos. Zygotes were treated with different concentrations of Ge-132 (0, 100, 200 and 400 μg/ml). All of the Ge-132 treatment groups displayed greater total cell numbers after IVC (98.1, 98.5 and 103.4, respectively) compared with the control group (73.9). The 200 μg/ml Ge-132 treatment group exhibited significantly increased intracellular GSH levels compared with the control group, whereas the ROS generation levels decreased in Ge-132 dose-dependent manner (P < 0.05). The mRNA expression levels of the KEAP1 gene and proapoptotic genes BAX and CASPASE3 were lower in the Ge-132 treated blastocysts compared with the control group (P < 0.05). The percentages of apoptotic and necrotic cells in the Ge-132 treated embryos on day 2 (48 h) were significantly lower than the untreated embryos (9.1 vs. 17.1% and 0 vs. 2.7%, respectively). In the day 7 blastocysts, the percentages of apoptotic cells in 200 µg/ml Ge-132 treated group were lower compared to controls (1.6 vs. 2.5%). More KEAP1 protein was found to be localized in cytoplasm of the 200 μg/ml Ge-132 treated blastocysts, whereas KEAP1 protein was predominantly nuclei in the control blastocysts. These results indicate that the developmental competence of embryos cultured under Ge-132 treatment may be associated with KEAP1 signaling cascades involved in oxidative stress and apoptosis during porcine preimplantation embryo development.

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“…Moreover, in its water‐soluble monomeric triol form, Ge‐132 is able to interact with a number of physiological substances: nucleic acids,[8c] monosaccharides etc. Recently a complex of adrenaline with Ge‐132 (Scheme ) have been isolated and structurally characterized . By analogy with the complex of adrenaline with GeO 2 , adrenaline‐Ge‐132 adduct could be expected to have a reduced antioxidant activity relative to the initial adrenaline.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Properties of Adrenaline in the Presence of Ge‐132

et al. 2019

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Using cyclic voltammetry, UV and 1H NMR spectroscopy, we have investigated the effect of 2‐carboxyethylgermanium (Ge‐132), the most common germanium‐containing dietary supplement, on the antioxidant activity of adrenaline in aqueous solutions. The complex formed by adrenaline and Ge‐132 is oxidizable at 400 mV more positive potentials compared to non‐coordinated adrenaline which corresponds to its 9 kcal/mol more difficult oxidation. An equilibrium constant of the complex formation was estimated (1300 m–1). It was shown that at the concentrations <10–3 m the complex Ge‐132‐adrenaline is mostly dissociated to the initial compounds, and the influence of Ge‐132 on the antioxidant properties of adrenaline becomes significant only when the former is in excess. Considering that such concentrations are typical for physiological conditions, this fact can be significant in identifying the mechanism of the biological action of Ge‐132 and its interference with the biological catechols.

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Organogermanium Compound, Ge-132, Forms Complexes with Adrenaline, Atp and Other Physiological Cis -Diol Compounds

Abstract: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.

Cited by 24 publications

References 44 publications

Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts

Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts

Carboxyethylgermanium sesquioxide (Ge-132) treatment during <i>in vitro</i> culture protects fertilized porcine embryos against oxidative stress induced apoptosis

Antioxidant Properties of Adrenaline in the Presence of Ge‐132

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