Alexander Keisha, Hazegh Kelsey, Fang Fang, Sinchar Derek, Kiss Joseph E, Page Grier P, DʼAlessandro Angelo, Kanias Tamir
Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.
Vitalant Research Institute, Denver, Colorado, USA.
Transfusion. 2021 Jan;61(1):108-123. doi: 10.1111/trf.16141. Epub 2020 Oct 18.
Red blood cells (RBCs) derived from patients who receive testosterone replacement therapy (TRT) may be considered eligible for component production and transfusion. The aim of this study was to identify testosterone-dependent changes in RBC metabolism and to evaluate its impact on susceptibility to hemolysis during cold storage.
We characterized stored RBCs from two cohorts of TRT patients who were matched with control donors (no TRT) based upon sex, age, and ethnicity. We further evaluated the impact of testosterone deficiency (orchiectomy) on RBC metabolism in FVB/NJ mice. RBC metabolites were quantified by ultra-high-pressure liquid chromatography-mass spectrometry. RBC storage stability was determined in RBC units from TRT and controls by quantifying storage, osmotic, and oxidative hemolysis.
Orchiectomy in mice was associated with significant (P < 0.05) changes in RBC metabolism as compared with intact males including increased levels of acyl-carnitines, long-chain fatty acids (eg, docosapentaenoic acids), arginine, and dopamine. Stored RBCs from TRT patients exhibited higher levels of pentose phosphate pathway metabolites, glutathione, and oxidized purines (eg, hypoxanthine), suggestive of increased activation of antioxidant pathways in this group. Further analyses indicated significant changes in free fatty acids and acyl-carnitines in response to testosterone therapies. With regard to hemolysis, TRT was associated with enhanced susceptibility to osmotic hemolysis. Correlation analyses identified acyl-carnitines as significant modifiers of RBC predisposition to osmotic and oxidative hemolysis.
These observations provide new insights into testosterone-mediated changes in RBC metabolome and biology that may impact the storage capacity and posttransfusion efficacy of RBCs from TRT donors.
接受睾酮替代疗法（TRT）患者的红细胞（RBC）可被视为适合成分制备和输血。本研究的目的是确定睾酮依赖性红细胞代谢变化，并评估其对冷藏期间溶血易感性的影响。
我们对两组TRT患者储存的红细胞进行了特征分析，这两组患者在性别、年龄和种族方面与对照供者（未接受TRT）相匹配。我们进一步评估了睾酮缺乏（睾丸切除术）对FVB/NJ小鼠红细胞代谢的影响。通过超高压液相色谱-质谱法定量红细胞代谢物。通过定量储存、渗透和氧化溶血来确定TRT组和对照组红细胞单位的储存稳定性。
与完整雄性小鼠相比，小鼠睾丸切除术后红细胞代谢发生了显著（P < 0.05）变化，包括酰基肉碱、长链脂肪酸（如二十二碳五烯酸）、精氨酸和多巴胺水平升高。TRT患者储存的红细胞中磷酸戊糖途径代谢物、谷胱甘肽和氧化嘌呤（如次黄嘌呤）水平较高，提示该组抗氧化途径的激活增加。进一步分析表明，游离脂肪酸和酰基肉碱在睾酮治疗后发生了显著变化。关于溶血，TRT与渗透溶血易感性增强有关。相关性分析确定酰基肉碱是红细胞对渗透和氧化溶血易感性的重要调节因子。
这些观察结果为睾酮介导的红细胞代谢组和生物学变化提供了新的见解，这些变化可能会影响TRT供者红细胞的储存能力和输血后疗效。
