High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect on advanced lupus nephritis in New Zealand black/white F1 hybrid mice, and low-dose combination may be synergistic.
To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybrid (B/W) mice, and also to study the possible synergistic effect of both drugs, B/W mice were heminephrectomized at 32 weeks of age, and were divided into six groups. Each group of mice was treated with 50 microliters phosphate-buffered saline (PBS), 3 mg/kg methylprednisolone, 20 mg methylprednisolone, 0.6 mg DSP, 6 mg DSP, or with 3 mg methylprednisolone plus 0.6 mg DSP, s.c., four times per week for 8 weeks. Urine and blood samples (by tail vein venipuncture), as well as renal tissue specimens, were taken at 32 and 40 weeks of age. The degree of proteinuria, and serum anti-DNA activity (by ELISA) were determined. Renal specimens were evaluated with light- and immunofluorescence (C3)-microscopy, the degree of pathological changes being semi-quantitated and expressed as total light-microscopy (LM) and immunofluorescence (IF) scores. The survival rate at 40 weeks of age was significantly elevated in 0.6 mg DSP, 6 mg DSP, and methylprednisolone + DSP groups of mice compared with the control group. The appearance rate of significant post-treatment proteinuria was comparable among all groups. The difference (post-treatment titre--pretreatment titre) of serum anti-DNA activity in the 6 mg DSP and methylprednisolone + DSP groups were significantly less, while that of the 3 mg methylprednisolone group was greater compared with the control level. As for the total LM score, the levels significantly decreased in the 6 mg DSP, methylprednisolone + DSP and 3 mg methylprednisolone groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Okubo
M
M
Department of Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Inoue
K
K
Amemiya
K
K
Kobayashi
N
N
Masaki
Y
Y
Kamata
K
K
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D006824:Hybridization, Genetic; D008181:Lupus Nephritis / Q000188:drug therapy*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008814:Mice, Inbred NZB
D006146:Guanidines; C037258:gusperimus; D008775:Methylprednisolone