Antioxidant Activity of Ge-132, a Synthetic Organic Germanium, on Cultured Mammalian Cells

Wada, Takeyoshi; Hanyu, Takashi; Nozaki, Kota; Kataoka, Kosuke; Tomoro, Kawatani; Asahi, Toru; Sawamura, Naoya

doi:10.1248/bpb.b17-00949

Cited by 29 publications

(37 citation statements)

References 34 publications

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“…The results confirmed that THGP also significantly suppresses cell death due to prolonged oxidative stress and indicate that THGP exerts an inhibitory effect on oxidative stress-induced cell death. It has been reported that THGP suppresses cell death caused by oxidative stress 28 , and Wada et al . found that THGP (Ge-132) exerts a cell proliferative effect by increasing the intracellular ATP content.…”

Section: Results and Disccusionmentioning

confidence: 99%

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 Disccusionmentioning

confidence: 99%

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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“…This study demonstrates that THGP does not influence tyrosinase activity or the expression of genes involved in melanogenesis (Figure 5). In addition, previous studies have demonstrated that THGP exerts antitumor and antioxidant effects; thus, the side effects of THGP are likely limited [39,40,41,42]. Furthermore, because THGP did not affect cell proliferation at concentrations up to 5000 μM, THGP is considered safe up to this concentration (Figure 3).…”

Section: Discussionmentioning

confidence: 95%

The Organogermanium Compound THGP Suppresses Melanin Synthesis via Complex Formation with L-DOPA on Mushroom Tyrosinase and in B16 4A5 Melanoma Cells

Azumi

Takeda

Shimada

et al. 2019

IJMS

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The organogermanium compound 3-(trihydroxygermyl)propanoic acid (THGP) has various biological activities. We previously reported that THGP forms a complex with cis-diol structures. L-3,4-Dihydroxyphenylalanine (L-DOPA), a precursor of melanin, contains a cis-diol structure in its catechol skeleton, and excessive melanin production causes skin darkening and staining. Thus, the cosmetic field is investigating substances that suppress melanin production. In this study, we investigated whether THGP inhibits melanin synthesis via the formation of a complex with L-DOPA using mushroom tyrosinase and B16 4A5 melanoma cells. The ability of THGP to interact with L-DOPA was analyzed by 1H-NMR, and the influence of THGP and/or kojic acid on melanin synthesis was investigated. We also examined the effect of THGP on cytotoxicity, tyrosinase activity, and gene expression and found that THGP interacted with L-DOPA, a precursor of melanin with a cis-diol structure. The results also showed that THGP inhibited melanin synthesis, exerted a synergistic effect with kojic acid, and did not affect tyrosinase activity or gene expression. These results suggest that THGP is a useful substrate that functions as an inhibitor of melanogenesis and that its effect is enhanced by combination with kojic acid.

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“…Generally, the immunostimulation property of organic germanium is deemed to be the foundation of its various therapeutic effects, such as anticancer, antiaging, antiviral and antiinflammatory effects-areas in which immune function plays a key role. The immune function activation mechanism of organic germanium is established by enriching the oxygen supply [48,76,77], detoxifying heavy metal elements [48,[78][79][80], scavenging reactive oxygen species (ROS) [81][82][83] and increasing reduced glutathione (GSH) levels [81,84]. El-Din [85] reported that organic germanium showed radical scavenging activity immediately after tumor inoculation and γ-irradiation exposure, resulting in the suppression of tumor growth and in the reduction of cellular injury from γ-irradiation-induced toxicity, which were attributable to the inhibition of the cascade reaction of membrane lipid peroxidation.…”

Section: Plos Onementioning

confidence: 99%

Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights

et al. 2020

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Germanium has long been considered a therapeutic agent with anticancer, antitumor, antiaging, antiviral and anti-inflammatory effects. Numerous clinical studies have explored the promising therapeutic effects of organic germanium on cancer, arthritis and senile osteoporosis. The immune activation property of organic germanium is considered the foundation of its various therapeutic effects. However, previous human clinical studies investigating immune activation with organic germanium compounds have certain limitations, as some studies did not strictly follow a randomized, double-blind, placebo-controlled design. To build a more clinically substantiated foundation for the mechanism underlying its immunostimulation, we structured by far the most rigorous clinical study to-date with a group of 130 human subjects to examine changes in immune profiles following germanium supplementation. We used Bio-Germanium, an organic germanium compound naturally synthesized via a yeast fermentation process. An 8-week randomized, double-blind, placebo-controlled study was conducted with 130 subjects with leukocyte counts of 4-8 (×10 3 /μL) divided into the Bio-Germanium group and the placebo group. Anthropometric measurements; blood collection; biochemical analysis; urinalysis; and natural killer cell activity, cytokine and immunoglobulin assays were conducted. Results showed the Bio-Germanium group exhibited NK cell activity increases at effector cell:target cell (E:T) ratios of 50:1, 10:1, 5:1 and 2.5:1 (12.60±32.91%, 10.19±23.88%, 9.28±16.49% and 7.27±15.28%, respectively), but the placebo group showed decreases (P<0.01). The difference in the IgG1 change from baseline to follow-up between the Bio-Germanium and placebo groups was significant (P = 0.044). Our results and earlier clinical study of Bio-Germanium confirm that Bio-Germanium acts as an effective immunostimulant by increasing the cytotoxicity of NK cells and activating immunoglobulin, B cells and tumor necrosis factor (TNF)-α (P<0.05). As we have added newly discovered clinical findings for germanium's immunostimulation mechanism, we

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Antioxidant Activity of Ge-132, a Synthetic Organic Germanium, on Cultured Mammalian Cells

Cited by 29 publications

References 34 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

The Organogermanium Compound THGP Suppresses Melanin Synthesis via Complex Formation with L-DOPA on Mushroom Tyrosinase and in B16 4A5 Melanoma Cells

Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights

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