Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis.

BACKGROUND: Cisplatin chemotherapy often causes acute kidney injury in cancer patients. The causative mechanisms of cisplatin-induced acute kidney injury include renal inflammation, activation of p53 tumour suppressor protein and tubular apoptosis. Luteolin, a flavone found in medicinal herbs and plants, has been reported to exhibit anti-inflammatory, antioxidant and anticarcinogenic activities. The purpose of this study was to investigate the anti-apoptotic effect of luteolin on cisplatin-induced acute kidney injury and the molecular mechanism. METHODS: C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without treatment with luteolin (50 mg/kg for 3 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of luteolin on cisplatin-induced expression of renal p53, PUMA-α and Bcl-2 family proteins were evaluated. RESULTS: Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. Treatment of cisplatin-treated mice with luteolin significantly improved renal dysfunction, reducing tubular cell damage, oxidative stress and apoptosis. Examination of molecules involving apoptosis of the kidney revealed that treatment of cisplatin increased the levels of p53 and its phosphorylation, PUMA-α, Bax and caspase-3 activity that were significantly decreased by treatment with luteolin. CONCLUSION: These results indicate that cisplatin induces acute kidney injury by regulation of p53-dependent renal tubular apoptosis and that luteolin ameliorates the cisplatin-mediated nephrotoxicity through down-regulation of p53-dependent apoptotic pathway in the kidney.

Cyclic mechanical strain promotes transforming-growth-factor-beta1-mediated cardiomyogenic marker expression in bone-marrow-derived mesenchymal stem cells in vitro.

Cardiomyocytes in the heart reside in mechanically dynamic environments, such as those subject to cyclic mechanical strain. TGF-beta1 (transforming growth factor-beta1) stimulates cardiomyogenic marker expression of BMMSCs (bone-marrow-derived mesenchymal stem cells). In the present study, we tested the hypothesis that cyclic mechanical strain promotes TGF-beta1-mediated cardiomyogenic marker expression in BMMSCs in vitro. The mRNA expression of cardiac-specific genes was more up-regulated in BMMSCs cultured with a TGF-beta1 supplement and subjected to cyclic strain for 1 week than in BMMSCs cultured statically with a TGF-beta1 supplement. Immunocytochemical analyses and flow cytometric analysis showed that the proportions of cardiac troponin-I-positive cells and cardiac MHC (myosin heavy chain)-positive cells and the proportions of cells expressing tropomyosin respectively were increased to a greater extent by TGF-beta1with cyclic strain than by TGF-beta1 alone. These results showed that cyclic strain promotes TGF-beta1mediated cardiomyogenic marker expression in BMMSCs in vitro.