title: Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.
abstract: Metformin (MET), an anti-diabetic oral drug with antioxidant properties, has been proved to provide cardioprotective effects in patients with diabetic disease. However, the mechanism is unclear. This study aimd to investigate the effects of MET on the expressions of receptor for advanced glycation end products (RAGE) and high mobility group box 1 protein (HMGB1) in hyperglycemia-treated neonatal rat ventricular myocytes. Cardiocytes were prepared and cultured with high glucose and different concentrations of MET. The expressions of RAGE and HMGB1 were evaluated by Western blot analysis. The superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured. After 12 h-incubation, MET significantly inhibited the increase of MDA, TNF-α, LDH and CK levels induced by high glucose, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations while inhibiting the decrease of SOD level. Meanwhile, RAGE and HMGB1 expression were significantly increased induced by hyperglycaemia for 24 h (P < 0.05). MET inhibited the expressions of RAGE and HMGB1 in a dose-dependent manner, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations (P < 0.05). In conclusion, our study suggested that MET could reduce hyperglycemia-induced cardiocytes injury by inhibiting the expressions of RAGE and HMGB1.
authors.affiliation: Department of Endocrinology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.forename: Yuli
authors.initials: Y
authors.lastname: Cai
authors.forename: Bo
authors.initials: B
authors.lastname: Yi
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008687:Metformin / Q000008:administration & dosage*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D008687:Metformin; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase