Effects of the chelating agent DTPA on naturally accumulating metals in the body

• Published in: Toxicology letters Vol. 350; pp. 283 - 291
• Main Authors: Tominaga, Takako, Shimomura, Satoshi, Tanosaki, Sakae, Kobayashi, Nobuyoshi, Ikeda, Takashi, Yamamoto, Tetsuo, Tamura, Taiji, Umemura, Satoshi, Horibuchi-Matsusaki, Shiori, Hachiya, Misao, Akashi, Makoto
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.10.2021
• Subjects: chelating agent; DTPA; metalloenzyme; metals in the body; DTPA; metals in the body; chelating agent; metalloenzyme
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2021.08.001

Diethylenetriaminepentaacetate (DTPA) is the most widely used chelating agent for Pu and Am. Volunteers were assigned to receive intravenous injections or aerosol inhalations of 1 g of DTPA on days 1-4; volunteers received once daily injections of CaDTPA or ZnDTPA, CaDTPA inhalation as an aerosol, or CaDTPA injection on day 1 and ZnDTPA on days 2-4. CaDTPA injection or inhalation increased the excretion rates of Zn in urine with concomitantly reduced levels of serum Zn. Injection of CaDTPA reduced activities of serum alkaline phosphatase (AP) in parallel with the kinetics of Zn, whereas CaDTPA and ZnDTPA injection reduced activities of lactate dehydrogenase (LDH), and reduced activities of creatinine kinase (CK) were observed upon CaDTPA injection and its inhalation. Intravenous administration of CaDTPA and ZnDTPA enhanced excretion rates of Mn in urine, whereas transient reduction of Mn levels in serum was detected only via CaDTPA injection. Both CaDTPA and ZnDTPA transiently reduced levels of Mg in serum without affecting the excretion rates. On the other hand, both DTPAs increased excretion rates of toxic metals such as Pb and Cd, and CaDTPA also increased the rates of Hg. These results suggest that DTPA, and especially CaDTPA, removes essential metals and that the activities of these metalloenzymes are good indicators for the imbalance of essential metals during the DTPA administration. Our results also show that CaDTPA injection is more potent for removing these metals than ZnDTPA and inhalation of CaDTPA, and DTPA may be useful for the treatment of acute heavy metal poisoning with Pb, Cd, or Hg.