Suzuki Yuto, Taguchi Kazuaki, Okamoto Wataru, Enoki Yuki, Komatsu Teruyuki, Matsumoto Kazuaki
Faculty of Pharmacy, Keio University, Tokyo, Japan.
Faculty of Pharmacy, Keio University, Tokyo, Japan.
Toxicol Appl Pharmacol. 2023 May 1;466:116472. doi: 10.1016/j.taap.2023.116472. Epub 2023 Mar 17.
Sodium nitrite (NaNO) is a universal antidote for patients with cyanide poisoning. However, its use has serious drawbacks in terms of efficacy and safety. Herein, we present a promising antidote: methemoglobin (metHb)-albumin clusters. The metHb-albumin cluster is made by a metHb core wrapped by covalently bound human serum albumin. Spectral analyses proved that the metHb-albumin clusters possessed cyanide-binding properties similar to those of naked metHb. In vitro cell experiments showed that metHb-albumin clusters prevented the cyanide-induced inhibition of cytochrome c oxidase activity, resulting in a strong cytoprotective effect. In mice subjected to cyanide poisoning, metHb-albumin clusters reduced mortality and alleviated metabolic acidosis, while maintaining the activity of cytochrome c oxidase in organs; their efficacy was better than that of NaNO. Furthermore, the oxygen carrying capacity was maintained in poisoned mice treated with metHb-albumin clusters and was low in those treated with NaNO. These results indicate that metHb-albumin clusters could be a more effective and safer antidote against cyanide poisoning than NaNO.
亚硝酸钠（NaNO）是氰化物中毒患者的通用解毒剂。然而，其在疗效和安全性方面存在严重缺陷。在此，我们提出一种有前景的解毒剂：高铁血红蛋白（metHb）-白蛋白簇。高铁血红蛋白-白蛋白簇由包裹着共价结合的人血清白蛋白的高铁血红蛋白核心构成。光谱分析证明，高铁血红蛋白-白蛋白簇具有与裸高铁血红蛋白相似的氰化物结合特性。体外细胞实验表明，高铁血红蛋白-白蛋白簇可防止氰化物诱导的细胞色素c氧化酶活性抑制，从而产生强大的细胞保护作用。在氰化物中毒的小鼠中，高铁血红蛋白-白蛋白簇降低了死亡率并减轻了代谢性酸中毒，同时维持了器官中细胞色素c氧化酶的活性；其疗效优于亚硝酸钠。此外，用高铁血红蛋白-白蛋白簇治疗的中毒小鼠维持了携氧能力，而用亚硝酸钠治疗的小鼠则较低。这些结果表明，高铁血红蛋白-白蛋白簇可能是一种比亚硝酸钠更有效、更安全的氰化物中毒解毒剂。
