1.The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures.
Ali H1, Galal O2, Urata Y3, Goto S3, Guo CY3, Luo L3, Abdelrahim E4, Ono Y3, Mostafa E2, Li TS5. Biochem Biophys Res Commun. 2014 Sep 26;452(3):548-53. doi: 10.1016/j.bbrc.2014.08.112. Epub 2014 Aug 28.
Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30min before exposure to 50mGy γ-ray daily for 30days in sequences (cumulative dose of 1.5Gy). Mice were victimized 24h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit(+) stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60-90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment.
2.[Neuroprotective therapy for the treatment of acute ischemic stroke].
Naritomi H. Rinsho Shinkeigaku. 2001 Dec;41(12):1060-3.
Following cerebral ischemia, various biochemical reactions are provoked in a stepwise manner leading neuronal cells to ischemic death. The prevention of these biochemical reactions may exert neuroprotective actions and consequently reduce the magnitude of ischemic cerebral injury. On the basis of such a view, numerous neuroprotective drugs have been developed during the last decade. Quite a few drugs were found effective in reducing the infarct volume in experimental studies, and more than 15 of them were subjected to clinical phase III trials to see a therapeutic effectiveness. However, the results of phase III trials were disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and edaravone, all radical scavengers, were judged effective by small-sized trials with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact suggests that a one-point prevention of biochemical reactions by single drug is unable to rescue ischemic neuronal cells.
Leker RR1. Curr Opin Investig Drugs. 2003 Jan;4(1):83-90.
Chugai (the Japanese subsidiary of Roche) is developing nicaraven (Antevas), a water-soluble antioxidant, for the potential treatment of disorders caused by acute cerebrovascular diseases. A registration application was filed in April 1995, and in April 2002, nicaraven was still awaiting registration in Japan. By August 2002, Chugai had filed an NDA in Japan for the additional indication of subarachnoidal bleeding.
4.Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice.
Kawakatsu M1, Urata Y, Imai R, Goto S, Ono Y, Nishida N, Li TS. PLoS One. 2013;8(3):e60023. doi: 10.1371/journal.pone.0060023. Epub 2013 Mar 29.
Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been demonstrated to protect against ischemia-reperfusion injury in various organs. We investigated whether nicaraven can attenuate radiation-induced injury in hematopoietic stem/progenitor cells, which is the conmen complication of radiotherapy and one of the major causes of death in sub-acute phase after accidental exposure to high dose radiation. C57BL/6 mice were exposed to 1 Gy γ-ray radiation daily for 5 days in succession (a total of 5 Gy), and given nicaraven or a placebo after each exposure. The mice were sacrificed 2 days after the last radiation treatment, and the protective effects and relevant mechanisms of nicaraven in hematopoietic stem/progenitor cells with radiation-induced damage were investigated by ex vivo examination. We found that post-radiation administration of nicaraven significantly increased the number, improved the colony-forming capacity, and decreased the DNA damage of hematopoietic stem/progenitor cells.