Abstract
Methylglyoxal (MG), a reactive sugar-derived metabolite, exerts harmful effects by inducing oxidative stress, which aggravates a series of diabetic complications, including osteoporosis. The present study was performed to examine the effects of luteolin, a dietary polyphenolic flavonoid, on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. Pretreatment of MC3T3-E1 osteoblastic cells with luteolin prevented MG-induced cell death and production of tumor necrosis factor-alpha, intracellular reactive oxygen species, mitochondrial superoxide, and cardiolipin peroxidation. In addition, luteolin increased the levels of glutathione and nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inhibition of heme oxygenase-1 activity by MG. Pretreatment with luteolin prior to MG exposure reduced MG-induced mitochondrial dysfunction and increased the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and nitric oxide levels, suggesting that luteolin may induce mitochondrial biogenesis. Taken together, these observations indicated that luteolin has potential as a preventive agent against the development of diabetic osteopathy related to MG-induced oxidative stress in diabetes.