TY - JOUR
T1 - Toxicity study of DE-EDCP as a potential drug for cancer therapy
T2 - Toxicity profile of DE-EDCP
AU - Stanković, D. T.
AU - Ristić, S. M.
AU - Vukadinović, A. A.
AU - Mirković, M. D.
AU - Vladimirov, S. S.
AU - Milanović, Z.
AU - Radović, M.
AU - Mijović, M.
AU - Stanković, D. M.
AU - Sabo, T. J.
AU - Vranješ-Đurić, S. D.
AU - Janković, D.
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.
AB - It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.
KW - DE-EDCP
KW - DNA interaction
KW - biochemical analysis
KW - hematological parameters
KW - mice
KW - toxicity study
UR - http://www.scopus.com/inward/record.url?scp=85060129792&partnerID=8YFLogxK
U2 - 10.1177/0960327118819047
DO - 10.1177/0960327118819047
M3 - Article
C2 - 30558454
AN - SCOPUS:85060129792
SN - 0960-3271
VL - 38
SP - 466
EP - 481
JO - Human and Experimental Toxicology
JF - Human and Experimental Toxicology
IS - 4
ER -