General Information of the Drug (ID: ferrodrug0347)
Name
Diethylhexylphthalate
Synonyms
Diethylhexylphthalate; Di-(2-ethylhexyl) phthalate; CHEMBL402794; BDBM50371947; 1-O-[(2S)-2-ethylhexyl] 2-O-[(2R)-2-ethylhexyl] benzene-1,2-dicarboxylate

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Structure
3D MOL
Formula
C24H38O4
IUPAC Name
1-O-[(2R)-2-ethylhexyl] 2-O-[(2S)-2-ethylhexyl] benzene-1,2-dicarboxylate
Canonical SMILES
CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC
InChI
InChI=1S/C24H38O4/c1-5-9-13-19(7-3)17-27-23(25)21-15-11-12-16-22(21)24(26)28-18-20(8-4)14-10-6-2/h11-12,15-16,19-20H,5-10,13-14,17-18H2,1-4H3/t19-,20+
InChIKey
BJQHLKABXJIVAM-BGYRXZFFSA-N
PubChem CID
7057919
Full List of Ferroptosis Target Related to This Drug
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Driver
Responsed Disease Testicular injury ICD-11: NB9Z
Responsed Regulator Hypoxia-inducible factor 1-alpha (HIF1A) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
HIF-1 signaling pathway hsa04066
Cell Process Cell ferroptosis
In Vitro Model TM3 cells Normal Mus musculus CVCL_4326
TM4 cells Normal Mus musculus CVCL_4327
In Vivo Model
Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).

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Response regulation Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Injury of intra-abdominal organs ICD-11: NB91
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model hLCs (Liver cells)
In Vivo Model
Adult male and female fish were randomly assigned to 6 aquariums and acclimated to laboratory conditions for one week before DEHP exposure. There are 6 aquariums, where 3 aquariums were used for DEHP exposure as the treatment groups and 3 for control. Each aquarium was filled with 12 L of artificial seawater and 30 females and 30 males were assigned. Food residues and excrement were removed, and artificial water was renewed every day. The exposure groups were exposed to 10 ug/L DEHP, obtained by diluting the stock solution, and the control groups were treated with DMSO as a solvent control, in which the DMSO content did not exceed 0.01% (v/v).

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Response regulation Ferroptosis occurred in response to di (2-ethylhexyl) phthalate (DEHP) exposure, which resulted in DEHP-induced liver injury, an enrichment of the ferroptosis pathway along with iron overload, an increase in malondialdehyde (MDA) and lipid peroxidation (LPO) content, and a decrease in glutathione (GSH) levels.
References
Ref 1 Di-(2-ethylhexyl) phthalate exposure leads to ferroptosis via the HIF-1/HO-1 signaling pathway in mouse testes. J Hazard Mater. 2022 Mar 15;426:127807. doi: 10.1016/j.jhazmat.2021.127807. Epub 2021 Nov 24.
Ref 2 Acute exposure of di(2-ethylhexyl) phthalate (DEHP) induces immune signal regulation and ferroptosis in oryzias melastigma. Chemosphere. 2021 Feb;265:129053. doi: 10.1016/j.chemosphere.2020.129053. Epub 2020 Nov 23.