Effect of mizoribine on lupus nephropathy of New Zealand black/white F1 hybrid mice

Kamata, Kouju; Okubo, Michihito; Uchiyama, Takehiko; Masaki, Yoshihiko; Kobayashi, Yutaka; Tanaka, Toshio

doi:10.1016/0090-1229(84)90290-3

Cited by 24 publications

(15 citation statements)

References 19 publications

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“…Moreover, MZR inhibits the mixed lymphocyte reaction and the production of macrophage migration inhibitory factor [10], as well as inhibiting the passive immune reac tion. The immunosuppressive effect of MZR is thought to be associated with inhibition of helper T and B lympho cyte proliferation [11], MZR has been used experimentally for the treatment of Masugi nephritis and NZB/NZW FI lupus nephritis [12][13][14], In Masugi nephritis, MZR was shown to reduce both urinary protein excretion and serum anti-GBM anti body levels. In NZB/NZW FI mice, a decrement of the serum anti-DNA antibody level and prolongation of life span were observed.…”

Section: Discussionmentioning

confidence: 99%

Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

et al. 1996

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Mizoribine (MZR), a purine nucleoside antibiotic, is an effective immunosuppressive agent that prevents rejection reactions after kidney transplantation in humans. The present study was performed to examine the effect of MZR on nephrosis produced in rats given puromycin aminonucleoside (PAN). Urinary protein excretion in rats injected with PAN and MZR (PAN + MZR rats) was shown to be reduced significantly in comparison with rats given only PAN (PAN rats). Although mild hypoproteinemia persisted during the experimental period in PAN + MZR rats, no loss of body weight or state of malnutrition was observed. The reduction of serum IgG and C3 was reversed by administration of MZR. Polyethyleinamine (PEI) staining of renal sections showed increased numbers of anionic sites in PAN + MZR rats in comparison with PAN rats, suggesting that MZR improved the permselectivity of the glomerular basement membrane (GBM). Moreover, the production of thromboxane B₂ (TxB₂) was significantly inhibited in PAN + MZR rats compared with PAN rats. No serious adverse effects of MZR were observed after a large dose of the agent. It is possible that restoration of the charge barrier of the GBM damaged by PAN, or reduction of TxB₂ production by the glomeruli may underlie the reduction of protein excretion induced by administration of MZR.

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Section: Discussionmentioning

confidence: 99%

Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

et al. 1996

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“…Secondly, higher doses of MZR increase the area under the serum concentration-time curve (AUC) in lupus patients [7]: thus, the efficacy of MZR may depend on the peak serum level of the drug which, in turn, may be closely correlated with the AUC of the drug [9]. Thirdly, in an SLE mouse model, the intermittent administration (every other day) of MZR was effective for depressing anti-DNA antibody production [19]. Based on these rationales, we believe that the MZR-P protocol might be effective and safe for the treatment of SLE patients [8, 9, 13].…”

Section: Discussionmentioning

confidence: 99%

Mizoribine Treatment of Young Patients with Severe Lupus Nephritis: A Clinicopathologic Study by the Tohoku Pediatric Study Group

Tanaka

Oki²,

Tsuruga³

et al. 2008

Nephron Clin Pract

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Background: A novel purine synthesis inhibitor, mizoribine (MZR), with a similar activity to that of mycophenolate mofetil, was developed in Japan. We suspected that long-term oral MZR intermittent pulse therapy (MZR-P) might be more effective than the conventional daily MZR regimen due to the higher peak serum MZR levels that are achieved. Here, we examined the clinicopathologic efficacy of MZR-P treatment in 10 young patients with diffuse proliferative lupus nephritis (DPLN), including 3 patients who received MZR-P as their primary cytotoxic therapy. Methods: After their most recent renal flare-ups, all the patients were treated using MZR-P combined with oral prednisolone (PDN). MZR was administered as a single daily dose of 6–10 mg/kg per day (maximum dose of 500 mg) on 2 days of the week (Monday and Thursday) for at least 12 months or longer. The concomitantly administered PDN dose was gradually reduced. Results: The baseline characteristics of the patients were as follows: mean age 15 years; urinary protein/creatinine (Up/cr) ratio 1.57 ± 1.05 mg/mg; serum C3 level 50.3 ± 19.7 mg/dl; serum complement hemolytic activity (CH50) 18.1 ± 9.9 U/ml; serum anti-dsDNA antibody titer 177.5 ± 152.7 IU/ml; serum creatinine 0.6 ± 0.1 mg/dl, and European Consensus Lupus Activity Measurement (ECLAM) index 4.9 ± 2.6. Despite the gradual tapering of the PDN dose, marked improvements compared with the baseline values were observed at the last observation, mean interval of 29 months after the start of treatment: Up/cr ratio 0.19 ± 0.14; ECLAM index 1.3 ± 0.7 (p < 0.01); serum C3 level 76.5 ± 22.1 mg/dl; serum CH50 value 31.9 ± 8.7 U/ml, and anti-dsDNA antibody titer 34.2 ± 20.5 IU/ml (p < 0.05). The serum creatinine level remained within the normal range in all study participants. Post-treatment renal biopsies were performed in 5 of the patients; histology showed a marked attenuation of lesion progression. No serious adverse effects were observed. Conclusion: We believe that long-term MZR-P may prove to be a treatment of choice for young patients with DPLN. However, confirmation is needed as this preliminary study is limited by the small number of subjects, lack of controls, and its retrospective nature.

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“…THI is an imidazole derivative, as arc other agents with immunosuppressive actions including ii/athioprine [2], urocanic acid [4]. histamine [19,20] and mi/oribine [21,22]. At least some of these agents could act by scleclively stimulating the activity of regulatory T coll subsets, perhaps "suppressor cells*, thereby modulating immune responses.…”

Section: Discussionmentioning

confidence: 99%

Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutyIimidazole (THI), a component of caramel colouring III

Mandel

Koulmanda

Mackay

1992

Clinical and Experimental Immunology

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SUMMARY The effect of oral administration of THI, a compound present in ammonia caramel food colouring, was studied in spontaneous and induced murine diabetes mellitus. Continuous administration of THI at400 ppm in drinking water reduced the prevalence of spontaneous diabetes in female NOD/Lt mice from 63% in untreated controls to 8% in treated animals. Since cyclophosphamide (CP) accelerates and intensifies diabetes in NOD mice, we also studied the effect of THI in this model. Diabetes incidence was reduced from 100% in mice given only CP to 13–14% in mice given THI either concurrently or from 14 days previously. Histologically.THI greatly reduced the severity of insulitis. As measured by flow cytometry, all THI‐treated mice had a 60–80% reduction in splenic CD4+ and CD8+ T cells. THI‐treated mice showed no untoward effects and specifically no weight loss, or pathological changes in their livers, kidneys or lungs. However, there was moderate atrophy of the thymus cortex. THI is a small imidazole‐containing compound with structural similarity to histamine and urocanic acid, both known to have immunosuppressive properties. It is a widely used food additive with no known long‐term toxic effects al low dosage. Thus, THI could be a useful immunosuppressive agent.

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Effect of mizoribine on lupus nephropathy of New Zealand black/white F1 hybrid mice

Cited by 24 publications

References 19 publications

Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

Mizoribine Treatment of Young Patients with Severe Lupus Nephritis: A Clinicopathologic Study by the Tohoku Pediatric Study Group

Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutyIimidazole (THI), a component of caramel colouring III

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