Immunosuppressive Effect of Bredinin on Cell-Mediated and Humoral Immune Reactions in Experimental Animals

Kamata, Ken; Okubo, Michihito; E, Ishigamori; Masaki, Yoshihiko; Uchida, Hisanori; Watanabe, Kôji; Kashiwagi, Noboru

doi:10.1097/00007890-198302000-00007

Cited by 47 publications

(27 citation statements)

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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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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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“…In 2000, we described the cases of four patients with IMN and nephrotic syndrome who showed good outcomes with the use of the antimetabolite mizoribine, followed by low-dose prednisone treatment. 20 Mizoribine is one of the safest immunosuppressants, 21,22 and is a purine metabolism inhibitor manufactured in Japan that mimics the action of mycophenolate mofetil (MMF). 23 In 2004, we conducted a hospital-based prospective trial with this treatment regimen for consecutive patients with IMN and nephrotic-range proteinuria.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

Matsumoto¹,

Shimada²,

Nojima³

et al. 2013

Renal Failure

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Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria, Renal Failure, 35:7,[936][937][938][939][940][941] Background: Idiopathic membranous nephropathy (IMN) patients with persistent high-grade proteinuria are at the highest risk for developing end-stage renal failure. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone treatment in 4 IMN patients. The purpose of the present study was to further assess the effects of this combined treatment in a larger study group. Method: Thirteen patients with IMN and nephroticrange proteinuria received combined treatment. Mizoribine was initiated at a dose of 150 mg/ day, and 2-3 months later, 20 mg/day prednisone was added to the mizoribine regimen. The dosage of prednisone and/or mizoribine was tapered according to the urinary proteinto-creatinine ratio (P/C). We evaluated patient responses for up to 12 months after the initiation of combination therapy. Results: Before treatment, patient urinary P/C ranged from 3.7 to 15.9 g/g. Although these values did not decrease during mizoribine monotherapy, all patients showed dramatic P/C decreases over the course of combination therapy. At 3, 6, and 12 months after combination therapy, 15%, 31%, and 62% of patients attained complete remission, respectively, and all patients were in partial or complete remission 6 months after combination therapy. No notable side effects were observed. Conclusion: The addition of prednisone after mizoribine monotherapy can be beneficial for all IMN patients with nephrotic-range proteinuria syndrome. The risks associated with immunotherapy can be decreased by initially prescribing mizoribine alone, which might act as a base for establishing therapy, followed by low-dose prednisone treatment.

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“…It was originally isolated from a culture filtrate of Eupenicillium brefeldianium from a soil sample collected at Hachijo island, Tokyo. Primarily it was shown to have potent immunosuppressive activity in various studies [3], Its immunosuppressive action has been shown to be due to selective inhibition of T and B lymphocyte proliferation. Furthermore, MZR has been used on a trial basis for the treatment of intractable nephrotic syndrome, and its effects suggested a reduction of urinary protein excretion.…”

Section: Introductionmentioning

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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Immunosuppressive Effect of Bredinin on Cell-Mediated and Humoral Immune Reactions in Experimental Animals

Cited by 47 publications

References 0 publications

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

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

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

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