Prolonged administration enhances the renoprotective effect of pentoxifylline via anti-inflammatory activity in streptozotocin-induced diabetic nephropathy.
The beneficial effects of pentoxifylline (PTX), which has an anti-inflammatory and renoprotective effect in diabetic nephropathy, are not completely understood. This study investigates whether prolonged administration of PTX (40 mg/kg, per oral) is effective in streptozotocin-induced diabetic nephropathy. The amount of urinary protein was higher in the diabetic rats than in the control rats. The amount remained unchanged after 4 weeks and decreased after 8 weeks of PTX treatment. Accumulation of monocyte chemoattractant peptide-1 (MCP-1) and mouse monoclonal anti-monocyte/macrophage antibody (ED-1) positive cells was higher in untreated diabetic rats than in the control rats. PTX administration ameliorated the urinary MCP-1 excretion and interstitial infiltration of ED-1 positive cells at 4 weeks. Further, in diabetic rats, administration of PTX for 4 weeks inhibited the renal inflammatory reaction, and when administration for 8 weeks, it prevented proteinuria. These findings support the hypothesis that prolonged administration enhances the protective effects of PTX.
Han
Kum Hyun
KH
Department of Internal Medicine, Inje University College of Medicine Ilsan-Paik Hospital, Goyang, Korea.
Han
Sang Youb
SY
Kim
Han Seong
HS
Kang
Young Sun
YS
Cha
Dae Ryong
DR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000276:immunology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097382:CD68 Molecule
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D010431:Pentoxifylline; D012333:RNA, Messenger; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C491766:Ccl2 protein, rat