Schupp Nicole, Dette Eva Maria, Schmid Ursula, Bahner Udo, Winkler Michaela, Heidland August, Stopper Helga
Department of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Sep;378(3):283-91. doi: 10.1007/s00210-008-0310-y. Epub 2008 May 29.
Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation. AGE-associated fluorescence in plasma, and in the second study additionally, the antioxidative capacity of plasma was analyzed. Benfotiamine significantly lowered the genomic damage of PBLs in hemodialysis patients of both studies independent of changes in plasma AGE levels. The second study gave a hint to the mechanism, as the antioxidative capacity of the plasma of the treated patients clearly increased, which might ameliorate the DNA damage.
血液透析患者外周血淋巴细胞(PBLs)中的基因组损伤增加,癌症发病率也升高,这可能是由于尿毒症毒素(如晚期糖基化终产物,AGEs)的积累所致。由于维生素B1前体药物苯磷硫胺可降低实验性糖尿病中的AGE水平,且透析患者常患有维生素B1缺乏症,因此我们进行了两项连续的研究,对血液透析患者补充苯磷硫胺。在这两项研究中,基因组损伤均通过补充苯磷硫胺前及补充后三个时间点的PBLs微核频率来衡量。分析了血浆中与AGE相关的荧光,在第二项研究中还分析了血浆的抗氧化能力。在两项研究中,苯磷硫胺均显著降低了血液透析患者PBLs的基因组损伤,且与血浆AGE水平的变化无关。第二项研究提示了其机制,因为接受治疗患者的血浆抗氧化能力明显增强,这可能改善了DNA损伤。