Effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats.
The objective is to assess the effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats. Male Wistar rats, 8-week-old, were categorized into four groups, which were the control (n = 9), diabetes (n = 9), infliximab-treated diabetes (n = 10), and FR167653-treated diabetes (n = 9) groups. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg). Thereafter, infliximab was injected intraperitoneally once a month (5.5 mg/kg) and FR167653 was administered orally by mixing with the rat chow (0.08%). The effects of infliximab and FR167653 on urinary albumin excretion were observed for 12 weeks. Body weight, blood sugar, 24-h urinary TNF-alpha, and 24-h urinary albumin/creatinine ratio (Ualb/Ucr) levels were determined at 1, 4, 8, and 12 weeks after the STZ-injection. Treatment of rats with STZ caused a significant loss of body weight, as well as polyuria and hyperglycemia within 1 week, while the urinary excretions of albumin and TNF-alpha were increased. Neither infliximab nor FR167653 affected body weight or blood sugar levels, whereas both decreased urinary albumin excretion, together with a modest decrease in the urinary excretion of TNF-alpha. These results suggest a role of TNF-alpha in the pathogenesis of diabetic nephropathy and show that TNF-alpha inhibition is a potential therapeutic strategy.
Moriwaki
Yuji
Y
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, 663-8501 Hyogo, Japan. moriwaki@hyo-med.ac.jp
Inokuchi
Taku
T
Yamamoto
Asako
A
Ka
Tsuneyoshi
T
Tsutsumi
Zenta
Z
Takahashi
Sumio
S
Yamamoto
Tetsuya
T
D000419:Albuminuria; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000652:urine*; D000069285:Infliximab; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000652:urine*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; C104334:FR 167653; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab