| Co-Investigator(Kenkyū-buntansha) |
MORI Kazuyuki Hirosaki University School of Medicine, UROLOGY, instructor, 医学部, 助手 (40266903)
KAWAGUCHI Toshiaki Hirosaki University Hospital, UROLOGY, lecturer, 医学部附属病院, 講師 (20204696)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Recent studies have shown that nitric oxide(NO) synthases, particularly inducible nitric oxide synthase(i-NOS), are massively induced in acute rejection episodes following heart, liver, pancreas and kidney allotransplantation. Furthemore, tissue and cellular injury in grafts has been demonstrated to be mediated by peroxynitrite anion(ONOO-), a metabolite of NO as well as a potent biological oxidant. On the other hand, in chronic rejection of human renal allografts, ONOO-has been implicated in nitration and inactivation of manganese-superoxide dismutase(MnSOD), a radical scavenger. However, a detailed relationship between NO, i-NOS, ONOO-and MnSOD in acute rejection episodes remains elusive. The following results weve abtained using rat models. In rat renal allograft acute rejection, markedly increased levels of serum NO were observed, along with enhanced tissue i-NOS activity, together resulting in graft injury. The administration of Aminoguanidine(AG), a potent i-NOS inhibitor, suppressed the increase in serum NO levels, with concomitant mitigation of tissue injury and renal function impair ment. Furthermore, in the allograft group, MnSOD activity was significantly decreased compared to the isograft group, in parallel with increased inactivated tyrosine-nitrated MnSOD, thus leading to accumulation of ONOO-products(nitrotyrosine) in tubules accounting for graft injuries.
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