Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Pharmazie. 2020 May 1;75(5):218-222. doi: 10.1691/ph.2020.0341.
Previously, a significant elevation in the serum levels of iron (Fe) was observed within a few days after the initiation of cisplatin (CDDP)-based chemotherapy. To clarify the underlying mechanisms, the serum concentration of hepcidin, a negative regulator of Fe release, was determined in the clinical samples obtained from six patients with cancer. The result showed that the serum concentration of hepcidin in patients receiving CDDP-based chemotherapy was significantly increased after 4-6 days of treatment, in comparison to the baseline level, suggesting that aforementioned excessive systemic Fe was not explained by the change of serum hepcidin level. All these patients received antiemetic premedication. We next evaluated of the effects of Pt-containing drugs and prophylactic antiemetic dexamethasone medication on the serum concentration of trace metals in mice, and on the hepatic and renal concentration of trace metals. The serum concentrations of Fe, Cu, and Zn in the CDDP-treated and oxaliplatin-treated mice were not significantly altered in comparison to those of the vehicle-treated control group. The serum concentrations of Fe, Cu, and Zn were increased after 24 h of dexamethasone treatment, compared to those of the control group (P < 0.05). The hepatic concentration of Mn was significantly reduced, whereas those of Fe and Cu inclined to diminish. The present findings suggest that dexamethasone can partly contribute to the changes in the serum concentrations of trace metals during anticancer chemotherapy.
先前，在开始顺铂（CDDP）为基础的化疗后几天内，观察到血清铁（Fe）水平显著升高。为了阐明潜在的机制，在从六名癌症患者获得的临床样本中测定了铁调素的血清浓度，铁调素是铁释放的负调节剂。结果表明，接受 CDDP 为基础的化疗的患者的血清铁调素浓度在治疗后 4-6 天明显升高，与基线水平相比，表明上述过量的系统性铁不能用血清铁调素水平的变化来解释。所有这些患者都接受了止吐药的预处理。接下来，我们评估了含 Pt 的药物和预防性止吐药地塞米松对小鼠血清中痕量金属以及肝肾功能中痕量金属浓度的影响。与对照组相比，CDDP 处理和奥沙利铂处理的小鼠的血清铁、铜和锌浓度没有明显改变。与对照组相比，地塞米松处理 24 小时后，血清铁、铜和锌的浓度增加（P < 0.05）。锰的肝浓度显著降低，而铁和铜的浓度则倾向于减少。这些发现表明，地塞米松可能部分导致抗癌化疗期间痕量金属血清浓度的变化。
