Kenkichi Kanno, Fumikazu Okumura (*), Wataru Toriumi, Noriko Ishiyama,
Shinsuke Nishiyama and Kazuaki Naito
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50
Kawagishi, Toda, Saitama 335-8505, Japan
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: Glomerulonephritis, Nephrotoxic serum, Wistar-Kyoto rat, Antinephritic
agent, Proteinuria