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High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect on advanced lupus nephritis in New Zealand Black/White Fl hybrid mice, and low-dose combination may be synergistic

High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect... Abstract To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybnd (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 μl phosphate-buffered saline (PBS), 3 mg/kg methylprednisolone, 20 mg methylprednisolone, 0.6 mg DSP, 6 mg DSP, or with 3 mg methylpredniso lone plus 0.6 mg DSP, s.c., four times per week for 8 weeks. Urine and blood samples (by tail vein veni puncture), 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 deter mined. Renal specimens were evaluated with light- and immunofluorescence (C3) the degree of pathological changes being semi-quantitated and expressed as total light-microscopy (LM) and immuno fluorescence (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 compar able 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 methyl prednisolone 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 methylpredniso lone groups. The change in the total IF score was reduced only in the 6 mg DSP and methyl prednisolone + DSP groups compared with the control level. In conclusion, 6 mg DSP treatment produced consistent therapeutic effect on advanced nephropathy, and it surpassed the effect of low- or high-dose methyl prednisolone, which proved only marginal at best. Additionally, the combination of low-dose DSP and low-dose methylprednisolone acted synergistically, and the effect was comparable with that of high-dose DSP monotherapy. advanced lupus nephntis, combination therapy, 15-deoxyspergualin, methylprednisolone, New Zealand Black/White F1 hybnd mice This content is only available as a PDF. © 1993 European Dialysis and Transplant Association-European Renal Association http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nephrology Dialysis Transplantation Oxford University Press

High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect on advanced lupus nephritis in New Zealand Black/White Fl hybrid mice, and low-dose combination may be synergistic

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Publisher
Oxford University Press
Copyright
© 1993 European Dialysis and Transplant Association-European Renal Association
ISSN
0931-0509
eISSN
1460-2385
DOI
10.1093/ndt/8.8.720
Publisher site
See Article on Publisher Site

Abstract

Abstract To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybnd (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 μl phosphate-buffered saline (PBS), 3 mg/kg methylprednisolone, 20 mg methylprednisolone, 0.6 mg DSP, 6 mg DSP, or with 3 mg methylpredniso lone plus 0.6 mg DSP, s.c., four times per week for 8 weeks. Urine and blood samples (by tail vein veni puncture), 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 deter mined. Renal specimens were evaluated with light- and immunofluorescence (C3) the degree of pathological changes being semi-quantitated and expressed as total light-microscopy (LM) and immuno fluorescence (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 compar able 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 methyl prednisolone 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 methylpredniso lone groups. The change in the total IF score was reduced only in the 6 mg DSP and methyl prednisolone + DSP groups compared with the control level. In conclusion, 6 mg DSP treatment produced consistent therapeutic effect on advanced nephropathy, and it surpassed the effect of low- or high-dose methyl prednisolone, which proved only marginal at best. Additionally, the combination of low-dose DSP and low-dose methylprednisolone acted synergistically, and the effect was comparable with that of high-dose DSP monotherapy. advanced lupus nephntis, combination therapy, 15-deoxyspergualin, methylprednisolone, New Zealand Black/White F1 hybnd mice This content is only available as a PDF. © 1993 European Dialysis and Transplant Association-European Renal Association

Journal

Nephrology Dialysis Transplantation – Oxford University Press

Published: Jan 1, 1993

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