目的:阐明碘乙酸(IAA)对血液系统和电解质平衡的影响,因此进一步研究血常规参数和电解质水平的内在关系,IAA治疗后的主要血液学毒性作用及其模式。
方法:用0、6.25、12.5和25mg/kgIAA给48只21日龄雄性SPF级Sprague-Dawley(SD)大鼠灌胃31天。检测血常规和血浆无机离子水平后,使用Spearman相关系数来评估它们的关系。铁蛋白的变化,转铁蛋白,铁调素,通过酶联免疫吸附测定评估C反应蛋白和甘油醛-3-磷酸脱氢酶(GAPDH)。将EDock生物信息学工具应用于IAA和GAPDH的对接模型。
结果:与对照组相比,大剂量IAA对大鼠白细胞有明显的抑制作用,总数下降了51.12%,中性粒细胞对IAA特别敏感,数量减少了73.66%(P&lt;0.01),大鼠红细胞表现出小细胞低色素效应,血红蛋白和血细胞比容分别降低8.60%和8.70%,分别为(P<0.05)。但IAA对血小板影响不大。等离子铁,磷,锌和钾水平被显著抑制,而氯,通过IAA暴露,钠和镁水平明显升高。然而,血浆钙水平几乎不受IAA的影响。与对照相比,铁含量下降67.09%,而镁水平在高剂量组增加了131.82%(P<0.01)。总的来说,相关分析发现,血浆铁代谢与白细胞水平呈最强正相关,IAA暴露后红细胞和血小板系统参数,和白细胞数的相关系数,平均血红蛋白含量和平均红细胞体积分别为0.637、0.410和0.365(P<0.05)。与对照相比,在高剂量IAA组中,血浆C反应蛋白含量显著上调13.30%(P<0.05),血浆转铁蛋白和铁调节素水平也分别升高了12.73%和11.02%(P<0.05)。但是两组之间的血浆铁蛋白和GAPDH水平没有差异。对接模型显示IAA可以结合大鼠GAPDH的150个Cys活性位点。
结论:IAA不仅对大鼠白细胞和血浆电解质平衡有毒性作用,还会引起炎症和缺铁,导致较小的红细胞和较低的色素。
OBJECTIVE: To clarify the effect of iodoacetic acid(IAA) on the blood system and electrolyte balance, hence further study the intrinsic relation of blood routine parameters and electrolyte levels, major hematological toxicity effects and their pattern after IAA treatment.
METHODS: Forty-eight 21-day-old male SPF grade Sprague-Dawley(SD) rats were gavaged with 0, 6.25, 12.5 and 25 mg/kg IAA for 31 days. After detections of blood routine and plasma inorganic ion levels, Spearman correlation coefficients were performed to evaluate their relationship. Changes in ferritin, transferrin, hepcidin, C-reactive protein and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) were assessed by enzyme-linked immunosorbent assays. The EDock bioinformatics tool was applied to docking model of IAA and GAPDH.
RESULTS: Compared to the control, high-dose IAA exposure had obvious inhibition effect on rat leukocytes with the total number declined by 51.12%, and neutrophils were particularly sensitive to IAA with the number reduced by 73.66%(P<0.01), and rat erythrocytes exhibited a small cell low pigment effect with hemoglobin and hematocrit decreased by 8.60% and 8.70%, respectively(P<0.05). But IAA had little effects on the platelet. Plasma iron, phosphorus, zinc and potassium levels were repressed significantly, while chlorine, sodium and magnesium levels were elevated obviously through IAA exposure. However, plasma calcium levels were hardly affected by IAA. In comparison with the control, iron levels declined by 67.09%, whereas magnesium levels increased by 131.82% in the high-dose group(P<0.01). Overall, correlation analyses uncovered that plasma iron metabolism was most strongly and positively correlated with levels of leukocyte, erythrocyte and platelet system parameters after IAA exposure, and the correlation coefficients of leukocyte number, mean hemoglobin content and mean erythrocyte volume were 0.637, 0.410 and 0.365, respectively(P<0.05). Compared to the control, in the high-dose IAA group, the plasma content of C-reactive protein was significantly upregulated by 13.30%(P<0.05), and plasma levels of transferrin and ferromodulin were also respectively elevated by 12.73% and 11.02%(P<0.05). But plasma levels of ferritin and GAPDH did not differ between groups. The docking model exhibited that IAA could bind to the 150 Cys active site of rat GAPDH did.
CONCLUSIONS: IAA not only had toxic effects on rat leukocytes and the plasma electrolyte balance, but also generated inflammation and iron deficiency, leading to smaller erythrocytes and lower pigment.