Park Seo-Ro, Joo Hong-Gu
College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea.
Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea.
Korean J Physiol Pharmacol. 2022 May 1;26(3):157-164. doi: 10.4196/kjpp.2022.26.3.157.
Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs , mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs and . DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.
双硫仑(DSF)是一种乙醛脱氢酶抑制剂。DSF对实体瘤和血液系统恶性肿瘤具有强大的抗癌活性。尽管其对癌细胞的作用已得到证实,但关于DSF对骨髓细胞(BMs)毒性的研究却很少。DSF降低了BMs的代谢活性和线粒体膜电位。在亚组分析中,我们证实DSF不影响BMs的比例。此外,DSF显著损害了用粒细胞巨噬细胞集落刺激因子处理的BMs的代谢活性和分化,粒细胞巨噬细胞集落刺激因子是BMs重要的生长和分化因子。为了测定DSF对BMs的毒性,给小鼠注射了50mg/kg的剂量,该剂量用于抗癌作用。DSF在小鼠中未显著诱导BM毒性,可能被抗氧化防御机制所耐受。这是关于DSF对BMs影响的首次研究。DSF作为一种抗癌药物候选物已被广泛研究,许多抗癌药物会导致骨髓抑制。在这方面,本研究可为基础科学和临床研究人员提供有用信息。