Details

Autor(en) / Beteiligte

• Tada, Hisaya
• Ishii, Hirayuki
• Isogai, Sho

Titel

Protective effect of d-α-tocopherol on the function of human mesangial cells exposed to high glucose concentrations

Ist Teil von

• Metabolism, clinical and experimental, 1997-07, Vol.46 (7), p.779-784

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

1997

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Altered functions of mesangial cells (MCs) induced by high glucose levels are thought to play an important role in the pathogenesis of diabetic nephropathy. We investigated whether d-α-tocopherol (Toc), an antioxidant, can prevent malfunction of cultured human MCs induced by high-glucose media. Incubating MCs with 33 mmol/L glucose caused increased lipid peroxide (LPO) levels, disturbed cell replication, enhanced cytotoxicity, enhanced activity of the diacylglycerol (DGA)—protein kinase C (PKC) pathway, and overproduction of fibronectin and eicosanoids (6-keto prostaglanding F 1α [PGF 1α] and thromboxane B 2 [TXB 2]). The amount of LPO in MCs grown in 5 mmol/L glucose was reduced by the addition of Toc in a dose-dependent manner. Since the maximum effect of Toc on decreasing LPO was achieved at a concentration of 100 μmol/L, this dose was selected for the following experiments. Addition of Toc prevented increased LPO levels and [ 51Cr]-release from MCs induced by high-glucose media without affecting cell number. Toc decreased the total DAG level and PKC activity in membrane fractions in MCs cultured at both 5 and 33 mmol/L glucose. Furthermore, glucose-induced overproduction of fibronectin and eicosanoids from MCs was completely abolished by Toc. These results strongly suggest that Toc ameliorates glucose-induced malfunctions of MCs in vitro.