title: Glabridin Alleviates the Toxic Effects of Methylglyoxal on Osteoblastic MC3T3-E1 Cells by Increasing Expression of the Glyoxalase System and Nrf2/HO-1 Signaling and Protecting Mitochondrial Function.
abstract: Methylglyoxal (MG) contributes to the pathogenesis of age- and diabetes-associated complications. The present study investigated the effects of glabridin on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. MC3T3-E1 cells were treated with glabridin in the presence of MG, and markers of mitochondrial function and oxidative damage were examined. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin prevented MG-induced cell death, the production of intracellular reactive oxygen species and mitochondrial superoxides, cardiolipin peroxidation, and the production of inflammatory cytokines. The soluble form of receptor for advanced glycation end products (sRAGEs)/RAGE ratio increased upon MG treatment, but less so after pretreatment with glabridin, which also increased the level of reduced glutathione and the activities of glyoxalase I and heme oxygenase-1, all of which were reduced by MG. In addition, glabridin elevated the level of nuclear factor erythroid 2-related factor 2. These findings suggest that glabridin protects against MG-induced cell damage by inhibiting oxidative stress and increasing MG detoxification. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin reduced MG-induced mitochondrial dysfunction. Additionally, the nitric oxide level significantly increased upon glabridin pretreatment. Together, these data show that glabridin may potentially serve to prevent the development of diabetic bone disease associated with MG-induced oxidative stress.
authors.affiliation: Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
authors.affiliation: Research Institute of Endocrinology, Kyung Hee University Hospital , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
authors.affiliation: Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.|Department of Medicine, Graduate School, Kyung Hee University , Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: So Yong
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University , 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Suk
authors.initials: S
authors.lastname: Chon
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011765:Pyruvaldehyde / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D007529:Isoflavones; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010636:Phenols; D020011:Protective Agents; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D013481:Superoxides; D011765:Pyruvaldehyde; D051547:Heme Oxygenase-1; D007791:Lactoylglutathione Lyase; C107601:glabridin
keywords: cytotoxicity; glabridin; methylglyoxal; mitochondrial function; osteoblasts