Department of Analytical Chemistry, Faculty of Pharmacy, Erzincan Binali Yildirim University, 24100 Erzincan, Turkey.
Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey.
Ann Pharm Fr. 2023 Mar;81(2):220-232. doi: 10.1016/j.pharma.2022.09.004. Epub 2022 Sep 17.
The understanding of precision medicine, which aims for high efficacy and low toxicity in treatments, has gained more importance with omics technologies. In this study, it was aimed to reach new suggestions for low-toxicity treatment by clarifying the relationship between tamsulosin side effects and metabolome profiles.
Plasma samples of control and tamsulosin-treated rats were analyzed by LC-Q-TOF/MS/MS. MS/MS data was processed in XCMS software for the identification of metabolite and metabolic pathway analysis. Data were classified with MATLAB 2019b for multivariate data analysis. 34m/z values were found to be significantly different between the drug and control groups (P≤0.01 and fold analysis≥1.5) and identified by comparing METLIN and HMDB databases.
According to multivariate data analysis, α-Linolenic Acid, Thiamine, Retinoic acid, 1.25-Dihydroxyvitamin D3-26.23-Lactone, L-Glutamine, L-Serine, Retinaldehyde, Sphingosine 1-phosphate, L-Lysine, 23S.25-Dihydroxyvitamin D3, Sphinganine, L-Cysteine, Uridine 5'-diphosphate, Calcidiol, L-Tryptophan, L-Alanine levels changed significantly compared to the control group. Differences in the metabolisms of Retinol, Sphingolipid, Alanine-Aspartate-Glutamate, Glutathione, Fatty Acid, Tryptophan, and biosynthesis of Aminoacyl-tRNA, and Unsaturated Fatty Acid have been successfully demonstrated by metabolic pathway analysis. According to our study, vitamin A and D supplements can be recommended to prevent side effects such as asthenia, rhinitis, nasal congestion, dizziness and IFIS in the treatment of tamsulosin. Alteration of aminoacyl-tRNA biosynthesis and sphingolipid metabolism pathways during tamsulosin treatment is effective in the occurrence of nasal congestion.
Our study provides important information for tamsulosin therapy with high efficacy and low side effects in precision medicine.
随着组学技术的发展,精准医学对于治疗的高效性和低毒性的理解变得更加重要。本研究旨在通过阐明坦索罗辛副作用与代谢组学特征之间的关系,为低毒性治疗提供新的建议。
采用 LC-Q-TOF/MS/MS 分析对照和坦索罗辛处理大鼠的血浆样本。在 XCMS 软件中处理 MS/MS 数据,用于鉴定代谢物和代谢途径分析。使用 MATLAB 2019b 对数据进行分类,进行多变量数据分析。发现药物组和对照组之间有 34 个 m/z 值有显著差异(P≤0.01,倍数分析≥1.5),并通过比较 METLIN 和 HMDB 数据库进行鉴定。
根据多变量数据分析,与对照组相比,α-亚麻酸、硫胺素、视黄酸、1,25-二羟基维生素 D3-26,23-内酯、L-谷氨酰胺、L-丝氨酸、视黄醛、鞘氨醇 1-磷酸、L-赖氨酸、23S,25-二羟基维生素 D3、鞘氨醇、L-半胱氨酸、尿苷二磷酸、钙二醇、L-色氨酸、L-丙氨酸水平有显著变化。通过代谢途径分析成功证明了视黄醇、鞘脂、丙氨酸-天冬氨酸-谷氨酸、谷胱甘肽、脂肪酸、色氨酸和氨酰-tRNA 生物合成的生物合成以及不饱和脂肪酸的代谢发生了变化。根据我们的研究,在坦索罗辛治疗中,可以推荐补充维生素 A 和 D,以预防乏力、鼻炎、鼻塞、头晕和 IFIS 等副作用。在坦索罗辛治疗过程中,氨基酸酰-tRNA 生物合成和鞘脂代谢途径的改变对鼻塞的发生有影响。
本研究为精准医学中高效低副作用的坦索罗辛治疗提供了重要信息。