Carvalho Vinicius F, Barreto Emiliano O, Serra Magda F, Cordeiro Renato S B, Martins Marco A, Fortes Zuleica Bruno, e Silva Patrícia M R
Laboratório de Inflamação, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, no 4365, Manguinhos, CEP 21045-900, Rio de Janeiro, Brazil.
Eur J Pharmacol. 2006 Nov 7;549(1-3):173-8. doi: 10.1016/j.ejphar.2006.08.037. Epub 2006 Aug 26.
This study was undertaken to investigate the role of the aldose reductase in the refractoriness of diabetic rats to allergic inflammation. Wistar rats were actively sensitized with a mixture of Al(OH)3 plus ovalbumin and intrapleurally challenged with ovalbumin, 14 days later. Diabetes was induced by intravenous injection of alloxan into fasted rats, 7 days before sensitization, and the aldose reductase inhibitor zopolrestat was administered after 3 days of diabetes induction, once a day during 18 consecutive days. The treatment with zopolrestat restored antigen-induced protein extravazation and mast cell degranulation in the pleural cavity of diabetic sensitized rats. Zopolrestat also significantly reversed the suppression in the increase of total and specific levels of serum immunoglobulin E (IgE) noted in sensitized animals under conditions of diabetes. In addition, we noted that the drop in the pleural mast cell numbers as well as the increase in serum corticosterone levels in diabetic rats were inhibited by the drug. Our findings show that zopolrestat restored the hyporesponsiveness of diabetic rats to antigen provocation, in parallel with impairment of alloxan-induced mast cell depletion and hypercorticolism, indicating that polyol pathway activity seems to play an important role in these phenomena.
本研究旨在探讨醛糖还原酶在糖尿病大鼠对过敏性炎症反应性降低中的作用。Wistar大鼠用氢氧化铝加卵清蛋白混合物进行主动致敏，并在14天后经胸膜内注射卵清蛋白进行激发。在致敏前7天，通过对禁食大鼠静脉注射四氧嘧啶诱导糖尿病，并在诱导糖尿病3天后给予醛糖还原酶抑制剂唑泊司他，连续18天每天给药一次。唑泊司他治疗恢复了糖尿病致敏大鼠胸腔中抗原诱导的蛋白外渗和肥大细胞脱颗粒。唑泊司他还显著逆转了糖尿病条件下致敏动物血清免疫球蛋白E（IgE）总量和特异性水平升高的抑制作用。此外，我们注意到该药物抑制了糖尿病大鼠胸腔肥大细胞数量的减少以及血清皮质酮水平的升高。我们的研究结果表明，唑泊司他恢复了糖尿病大鼠对抗原激发的低反应性，同时伴有四氧嘧啶诱导的肥大细胞耗竭和高皮质醇血症的改善，这表明多元醇途径活性似乎在这些现象中起重要作用。
