Effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats

Acta Diabetol. 2007 Dec;44(4):215-8. doi: 10.1007/s00592-007-0007-6. Epub 2007 Sep 1.


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.

MeSH terms

  • Albuminuria
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Diabetes Mellitus, Experimental / urine*
  • Infliximab
  • Male
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / urine*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • FR 167653
  • Pyrazoles
  • Pyridines
  • Tumor Necrosis Factor-alpha
  • Infliximab