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

Abstract

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.

Challenges and opportunities in bringing nonbiological atoms to life with synthetic metabolism

“…Ge is advocated as a nontoxic alternative to toxic organotin reagents, and organogermanium compounds produced biologically could be an interesting alternative to the expensive chemical methods needed to obtain precursors for GeO 2 chemical vapor deposition. Some organogermanium compounds are of medical interest because they have promising anticancer properties and are used for the treatment of several other medical conditions, such as compound GEE-132 {repagermanium, bis[2carboxyethylgermanium(IV) sesquioxide]} [42]. Other Ge-containing organic compounds of interest include germatranes, which are cyclic molecules stabilized with a hypervalent Ge atom [43,44].…”

Base-stabilized formally zero-valent mono and diatomic molecular main-group compounds

“…The organic compounds of germanium have been investigated as anticancer, antiinflammatory, and immune-stimulating drugs. 131,132 Therefore, there is significant interest in synthesizing soluble sources of elemental germanium. After successful isolation of the NHC-stabilized disilicon(0) complex (90) by Robinson, 16 Jones and co-workers attempted to make an NHC-stabilized digermanium(0) complex from the reaction of IPr-GeCl 2 and KC 8 , but this route did not work.…”

Eriodictyol Attenuates H2O2-Induced Oxidative Damage in Human Dermal Fibroblasts through Enhanced Capacity of Antioxidant Machinery

“…Exposure to environmental and xenobiotic insults can disrupt the function of dermal fibroblasts through oxidative stress. Consequently, fibroblast dysfunction impairs the structural and mechanical integrity of the skin, eventually resulting in skin aging [5][6][7][8][9][10][11]. Therefore, using compounds that can promote the ability of dermal fibroblasts to counteract oxidative imbalance would be a promising strategy for inhibiting age-related skin problems.…”