Comparison of therapeutic efficacy between bortezomib and combination treatment of prednisolone and mycophenolate mofetil on nephritis in NZB/WF1 mice.
OBJECTIVE
We investigated the efficacy of bortezomib on nephritis in NZB/WF1 mice, and compared it to prednisolone (PL) and mycophenolate mofetil (MMF) treatment.


METHODS
Twenty-three NZB/WF1 mice were divided into four groups (untreated, 0.1 mg/kg and 1 mg/kg bortezomib-treated, and PL plus MMF-treated). Proteinuria, glomerular IgG deposition, cellular proliferation and histologic damages were evaluated.


RESULTS
In comparison with the untreated mice, 1 mg/kg bortezomib significantly reduced proteinuria and attenuated glomerular IgG deposition, cellular proliferation and histologic damages similar to PL plus MMF. 0.1 mg/kg bortezomib significantly improved glomerular IgG deposition and histologic damages except proteinuria or cellular proliferation compared to untreated mice. PL plus MMF showed significantly greater inhibition of cellular proliferation and histologic damage than 1 mg/kg bortezomib.


CONCLUSIONS
We found that 1 mg/kg bortezomib significantly improved lupus nephritis in NZB/WF1 mice. However, its efficacy did not exceed PL plus MMF treatment.
Lee
Sang-Won
SW
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Kim
Beom Seok
BS
D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002455:Cell Division; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*
D001897:Boronic Acids; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D011239:Prednisolone; D009173:Mycophenolic Acid