Sen Gargi, Biswas Debabrata, Ray Manju, Biswas Tuli
Indian Association for Cultivation of Science, Kolkata 700032, India.
Blood Cells Mol Dis. 2007 Nov-Dec;39(3):245-54. doi: 10.1016/j.bcmd.2007.06.008. Epub 2007 Jul 19.
Visceral leishmaniasis is associated with the reduced survival of erythrocytes, the cause of which remains to be fully explored. Here, we described the mechanism underlying the shortened lifespan of erythrocytes in visceral leishmaniasis and proposed a combination therapy with quercetin and hamster serum albumin towards its rectification. Decreased redox potential in erythrocytes followed by oxidative denaturation of hemoglobin and pathologic association of iron with the cell membrane facilitated premature hemolysis during leishmanial infection. Recently, we have reported the therapeutic efficacy of quercetin in arresting the enhanced destruction of erythrocytes in visceral leishmaniasis. Since serum albumin, the principal carrier protein for quercetin gets depleted in visceral leishmaniasis, the situation may compromise the efficacy of quercetin in this disease. We now report the use of quercetin-hamster serum albumin combination to increase the bioavailability of quercetin. The combination targeted hemoglobin oxidation and produced an effective attenuation of heme degradation. This led to decreased iron decompartmentalization, thereby increasing the life span of erythrocytes during leishmanial infection. Thus, we speculate that suppression of iron decompartmentalization, with the combination of quercetin and serum albumin might be a new approach in the prevention of reduced survival of erythrocytes in visceral leishmaniasis.
内脏利什曼病与红细胞存活率降低有关,其原因仍有待充分探究。在此,我们描述了内脏利什曼病中红细胞寿命缩短的潜在机制,并提出用槲皮素和仓鼠血清白蛋白联合治疗来纠正这一情况。利什曼原虫感染期间,红细胞氧化还原电位降低,随后血红蛋白发生氧化变性,铁与细胞膜发生病理性结合,从而促进了过早溶血。最近,我们报道了槲皮素在抑制内脏利什曼病中红细胞过度破坏方面的治疗效果。由于血清白蛋白是槲皮素的主要载体蛋白,在内脏利什曼病中会耗竭,这种情况可能会损害槲皮素在该疾病中的疗效。我们现在报道使用槲皮素 - 仓鼠血清白蛋白组合来提高槲皮素的生物利用度。该组合针对血红蛋白氧化,有效减弱了血红素降解。这导致铁的去分隔化减少,从而延长了利什曼原虫感染期间红细胞的寿命。因此,我们推测,槲皮素与血清白蛋白联合抑制铁的去分隔化,可能是预防内脏利什曼病中红细胞存活率降低的一种新方法。