Yu Hyerim, Jang Won-Jun, Jang Jung-Hee, Park Byoungduck, Seo Young Ho, Jeong Chul-Ho, Lee Sooyeun
College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea.
School of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea.
Forensic Sci Int. 2017 Dec;281:171-175. doi: 10.1016/j.forsciint.2017.11.004. Epub 2017 Nov 11.
Hair analysis has notably expanded its application as a bio-monitor for drug or toxicant exposure. Hair pigmentation is proposed as a major factor affecting drug incorporation into hair; however, the mechanisms underlying the incorporation of drugs into hair are still unclear. In the present study, the effect of hair pigmentation on drug incorporation into hair was examined using rats carrying hair with different melanin status and human cells (SK-Mel-28 cells, HaCaT cells and the co-cultured HaCaT cells with SK-Mel-28 cells) representing the main pigmentary unit in hair. Tramadol, a synthetic opioid analgesic, was selected as a model drug. The distribution of tramadol and its phase I (O-desmethyltramadol [ODMT], N-desmethyltramadol [NDMT] and N,O-didesmethyltramadol [NODMT]) and phase II metabolites (ODMT-glucuronide and NODMT-glucuronide) was investigated in non-pigmented and pigmented hair from Long-Evans rats. Moreover, the incorporation levels of ODMT and ODMT-glucuronide were compared in hair cells. The concentrations of tramadol and its phase I metabolites were significantly higher in pigmented rat hair while those of phase II metabolites did not showed any consistent significant difference depending on the status of hair pigmentation. ODMT was taken up to a greater extent than ODMT-glucuronide by SK-Mel-28 cells, HaCaT cells and the co-cultured HaCaT cells with SK-Mel-28 cells. Notably, the incorporated level of ODMT was higher in SK-Mel-28 cells than HaCaT cells and the concentration difference of ODMT was significantly larger than that of ODMT-glucuronide. This study clearly demonstrated that hair pigmentation played a role as a facilitating factor for the incorporation of basic compounds and provided insight into the drug incorporation process into hair.
毛发分析作为药物或毒物暴露的生物监测手段，其应用范围已显著扩大。毛发色素沉着被认为是影响药物掺入毛发的主要因素；然而，药物掺入毛发的潜在机制仍不清楚。在本研究中，利用携带不同黑色素状态毛发的大鼠以及代表毛发主要色素单元的人类细胞（SK-Mel-28细胞、HaCaT细胞以及SK-Mel-28细胞与HaCaT细胞的共培养细胞），研究了毛发色素沉着对药物掺入毛发的影响。选择合成阿片类镇痛药曲马多作为模型药物。研究了曲马多及其I相代谢物（O-去甲基曲马多[ODMT]、N-去甲基曲马多[NDMT]和N,O-二去甲基曲马多[NODMT]）以及II相代谢物（ODMT-葡萄糖醛酸苷和NODMT-葡萄糖醛酸苷）在Long-Evans大鼠无色素和有色素毛发中的分布。此外，还比较了毛发细胞中ODMT和ODMT-葡萄糖醛酸苷的掺入水平。曲马多及其I相代谢物在有色素的大鼠毛发中的浓度显著更高，而II相代谢物的浓度根据毛发色素沉着状态未显示出任何一致的显著差异。SK-Mel-28细胞、HaCaT细胞以及SK-Mel-28细胞与HaCaT细胞的共培养细胞对ODMT的摄取程度高于ODMT-葡萄糖醛酸苷。值得注意的是，SK-Mel-28细胞中ODMT的掺入水平高于HaCaT细胞，且ODMT的浓度差异显著大于ODMT-葡萄糖醛酸苷。本研究清楚地表明，毛发色素沉着作为碱性化合物掺入的促进因素发挥了作用，并为药物掺入毛发的过程提供了深入了解。
