Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin.
Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.
Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Yuseongdaero, Yuseong-gu, Daejeon, Republic of Korea.
Junghyun
J
Kim
Eunjin
E
Shon
Chan-Sik
CS
Kim
Jin Sook
JS
Kim
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008840:Microfilament Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D007004:Hypoglycemic Agents; D008840:Microfilament Proteins; C503969:Synpo protein, rat; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008687:Metformin; D003849:Deoxyguanosine