Anwar Attia, Marini Marina, Abruzzo Provvidenza Maria, Bolotta Alessandra, Ghezzo Alessandro, Visconti Paola, Thornalley Paul J, Rabbani Naila
a Warwick Medical School, Clinical Sciences Research Laboratories , University of Warwick, University Hospital Coventry , Coventry , UK.
b Department of Experimental, Diagnostic and Specialty Medicine , School of Medicine, University of Bologna , Bologna , Italy.
Free Radic Res. 2016 Nov;50(sup1):S85-S90. doi: 10.1080/10715762.2016.1239821. Epub 2016 Nov 2.
AIMS/HYPOTHESIS: To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage.
27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined.
Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower-upper quartile]): autistic children - 6.60 nM (4.48-8.91) and 7.00 nM (5.51-8.55), and healthy controls - 6.82 nM (4.47-7.02) and 6.82 nM (5.84-8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81-8.52) versus 9.00 nM (8.41-10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged.
CONCLUSIONS/INTERPRETATION: Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host-microbe homeostasis.
目的/假设:通过分析自闭症儿童和健康对照者的血浆和尿液来评估硫胺素及相关代谢物状态,研究其与临床特征的相关性以及与氧化损伤血浆蛋白标志物的联系。
招募了27名自闭症儿童(21名男性和6名女性)和21名年龄匹配的健康对照儿童(15名男性和6名女性)。测定了血浆和尿液中硫胺素及相关磷酸化代谢物的浓度以及血浆中双酪氨酸、N-甲酰犬尿氨酸和3-硝基酪氨酸的蛋白含量。
两个研究组的血浆硫胺素和硫胺素单磷酸浓度相似(中位数[下四分位数-上四分位数]):自闭症儿童分别为6.60 nM(4.48 - 8.91)和7.00 nM(5.51 - 8.55),健康对照者分别为6.82 nM(4.47 - 7.02)和6.82 nM(5.84 - 8.91)。与健康对照者相比,自闭症儿童的硫胺素焦磷酸(TPP)降低了24%:分别为6.82 nM(5.81 - 8.52)和9.00 nM(8.41 - 10.71),p < 0.01。两组之间硫胺素的尿排泄量和硫胺素的肾分数清除率没有变化。临床标志物与血浆和尿液硫胺素浓度之间未观察到相关性。自闭症谱系障碍(ASD)患者血浆蛋白双酪氨酸含量增加了88%。其他氧化标志物未改变。
结论/解读:自闭症儿童的血浆和尿液硫胺素水平正常,而血浆TPP浓度降低。后者可能与TPP的组织处理异常和/或肠道微生物群的吸收有关,这值得进一步研究。血浆蛋白双酪氨酸增加可能反映了双氧化酶活性增加,以应对黏膜免疫和宿主-微生物稳态的变化。