Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat.
Recent reports have shown that thiazolidinediones have preventive effects on urinary albumin excretion in diabetes. However, the mechanism leading to these effects has not yet been elucidated. We studied here the effects of thiazolidinediones on albuminuria and hemodynamic and morphological changes in the kidneys of streptozotocin (STZ)-induced diabetic spontaneous hypertensive rats (SHRs). Diabetes was induced in SHRs by intravenous injection of STZ (50 mg/kg). The diabetic SHRs were divided into the following 3 groups: (1) STZ-SHRs given normal chow (STZ), (2) STZ-SHRs given chow mixed with 0.1% troglitazone (STZ + tro), and (3) STZ-SHRs given chow mixed with 0.001% pioglitazone (STZ + pio). Three groups of nondiabetic SHRs were also investigated: (4) SHR, (5) tro, and (6) pio. We evaluated the urinary albumin excretion rate (AER) every 4 weeks. After 12 weeks of treatment, the animals were killed and renal morphological examinations were performed. Thiazolidinediones did not affect blood pressure or blood glucose levels. Urinary AER were markedly increased in STZ-SHRs. After 12 weeks of treatment with thiazolidinediones, the urinary AER was significantly decreased while creatinine (Cr) clearance was left unchanged. Histologically, the loss of anionic sites of glomerular basement membranes (GBM) evaluated with polyetyleneimine was suppressed significantly in the diabetic SHRs treated with thiazolidinediones. In conclusion, administration of thiazolidinediones in diabetic SHRs decreased the urinary AER and suppressed the loss of anionic sites of GBM without affecting blood pressure, blood glucose levels, or Cr clearance. These results clarify the novel therapeutic action of thiazolidinediones on diabetic nephropathy.
Yamashita
Haruhisa
H
First Department of Internal Medicine, School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
Nagai
Yukihiro
Y
Takamura
Toshinari
T
Nohara
Erika
E
Kobayashi
Ken-ichi
K
D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002839:Chromans / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012016:Reference Values; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D003404:Creatinine; D000077288:Troglitazone