Renal podocyte apoptosis in Zucker diabetic fatty rats: involvement of methylglyoxal-induced oxidative DNA damage.

Methylglyoxal (MGO) is a cytotoxic metabolite produced by in-vivo glycolysis that may result in diabetic complications. The aim of this study was to determine whether MGO and oxidative stress caused apoptosis of renal podocytes in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes mellitus. Male ZDF rats aged 21 weeks developed marked hyperglycaemia with proteinuria and albuminuria. Immunohistochemical evaluation of sections of kidney demonstrated expression of MGO and 8-hydroxydeoxyguanosine (8-OHdG) in the podocytes of both normoglycaemic and diabetic rats. Podocyte apoptosis was shown through application of the TUNEL method. These findings suggest that expression of MGO and 8-OHdG is caused by hyperglycaemia, and that this expression is associated with the observed apoptosis of podocytes and is related to diabetic nephropathy.

Kim J ，Sohn E ，Kim CS ，Kim JS ... -  《-》

Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy.

Susztak K ，Raff AC ，Schiffer M ，Böttinger EP ... -  《DIABETES》

Extract of the aerial parts of Aster koraiensis reduced development of diabetic nephropathy via anti-apoptosis of podocytes in streptozotocin-induced diabetic rats.

Advanced glycation end products (AGEs) is produced from glycolysis in vivo, which may result in diabetic nephropathy. Podocyte loss has been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the protective effects of Aster koraiensis extract (AKE), on the damage of renal podocytes in streptozotocin (STZ)-induced diabetic rats. AKE (100, 200mg/kg per day) was given to diabetic rats for 13weeks. Blood glucose, glycated haemoglobin (HbA1c), proteinuria and albuminuria were examined. Kidney histopathology, AGEs accumulation, apoptosis, and expression of Bax and Bcl-2 also were examined. In 20-week-old STZ-induced diabetic rats, severe hyperglycemia was developed, and proteinuria and albuminuria were markedly increased. TUNEL-positive signals were highly detected in glomeruli of STZ-induced diabetic rats. However, AKE reduced proteinuria and albuminuria in diabetic rats. AKE prevented AGEs deposition and podocyte apoptosis. Expression of Bax and Bcl-2 protein were restored by AKE treatment in the renal cortex. These results suggested that AKE has an inhibitory effect of AGE accumulation and anti-apoptotic effect in the glomeruli of diabetic rat. AKE could be beneficial in preventing the progression of diabetic nephropathy.

Sohn E ，Kim J ，Kim CS ，Kim YS ，Jang DS ，Kim JS ... -  《-》

Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin‑induced diabetic rats and its active compound emodin inhibits methylglyoxal‑mediated glycation of proteins.

Sohn E ，Kim J ，Kim CS ，Jo K ，Kim JS ... -  《-》

Spironolactone inhibits hyperglycemia-induced podocyte injury by attenuating ROS production.

Toyonaga J ，Tsuruya K ，Ikeda H ，Noguchi H ，Yotsueda H ，Fujisaki K ，Hirakawa M ，Taniguchi M ，Masutani K ，Iida M ... -  《-》