Nephrotoxic serum-induced nephritis in Wistar-Kyoto rats: a model to evaluate antinephritic agents.
We investigated nephrotoxic serum (NTS)-induced glomerulonephritis in Wistar-Kyoto (WKY) rats as a model to evaluate antinephritic agents. WKY rats required only a small amount of NTS to induce crescentic glomerulonephritis and the rats progressively lost their renal function in a few weeks. In a comparative study with WKY and Sprague-Dawley (SD) rats, WKY rats showed a normal distribution pattern in the severity of proteinuria with a small variance. While SD rats needed a much higher amount of NTS to exhibit a comparable proteinuria which was not normal and had a large variance. The effects of clinically available antinephritic drugs, methylprednisolone, cyclophosphamide and cyclosporin A, were studied in both strains. In WKY rats, these drugs significantly inhibited the proteinuria, glomerular histological changes and decrease in creatinine clearance. On the other hand, such significant inhibitory effects on proteinuria were not observed with any of these drugs in SD rats. In conclusion, NTS nephritis in WKY rats may prove to be a useful model for studying antinephritic agents.
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
K
K
Kanno
F
F
Okumura
W
W
Toriumi
N
N
Ishiyama
S
S
Nishiyama
K
K
Naito
D000818:Animals; D001485:Basement Membrane / Q000737:chemistry / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014118:Toxins, Biological / Q000009:adverse effects* / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014118:Toxins, Biological; D016572:Cyclosporine; D003520:Cyclophosphamide; D011239:Prednisolone