Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0225)

Name	Nickel Chloride
Synonyms	NICKEL CHLORIDE; 7718-54-9; Nickel dichloride; dichloronickel; Nickelous chloride; NiCl2; Nickel(2+) chloride; Nickel(II) chloride anhydrous; Nichel(II) chloride; 37211-05-5; Nickel chloride (NiCl2); Nickel dichloride (nicl2); Nickel(II) chloride (1:2); CCRIS 1788; HSDB 860; Nickel (II) chloride; EINECS 231-743-0; EINECS 253-399-0; NSC 254532; UNII-696BNE976J; CHEBI:34887; 696BNE976J; MFCD00011142; NSC254532; NSC-254532; (NiCl2); [NiCl2]; EC 231-743-0; Nickel(II) chloride, anhydrous; dichloro nickel; dichloronickel(II); NI(II) chloride; dichloronickel (II); nickel-(II)-chloride; nickel (11) chloride; WLN: NI G2; Nickel(II) chloride, 98%; Nickel(II) chloride, ultra dry; QMMRZOWCJAIUJA-UHFFFAOYSA-L; FT-0689065; FT-0689074; Q29397; Nickel(II) chloride, LR, 44.6-46% Ni basis; Nickel(II) chloride, anhydrous, powder, 99.99% trace metals basis Click to Show/Hide
Status	Investigative
Drug Type	Small molecular drug
Structure
Structure	3D MOL 2D MOL
Formula	Cl2Ni
IUPAC Name	dichloronickel
Canonical SMILES	Cl[Ni]Cl
InChI	InChI=1S/2ClH.Ni/h2*1H;/q;;+2/p-2
InChIKey	QMMRZOWCJAIUJA-UHFFFAOYSA-L
PubChem CID	24385
TTD Drug ID	D08MKF

Full List of Ferroptosis Target Related to This Drug

Prostaglandin G/H synthase 2 (PTGS2)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target			[1]
Target for Ferroptosis	Marker
Responsed Disease	Drug-induced or toxic liver disease	ICD-11: DB95	Disease Info
Pathway Response	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hLCs (Liver cells)
In Vivo Model	Totally 128 7-week-old ICR male mice (22-25 g) were provided by Dashuo Biological Technology (Chengdu, China). The animals were divided into four groups (32 mice per group) randomly. The mice in the three experimental groups were gavage administered with Ni (NiCl2·6H2O) at doses of 7.5, 15, and 30 mg/kg body weight respectively, while those in the control group were given distilled water. The Ni dose adopted here was determined according to the value of median lethal dose (LD50, 306.11 mg/kg) attained in the research on acute oral toxicity of male mice. We selected 1/40, 1/20 and 1/10 LD50 (306.11 mg/kg) of NiCl2 in this study. Click to Show/Hide
Response regulation	Nickel chloride caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice.

Phospholipid hydroperoxide glutathione peroxidase (GPX4)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target			[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Drug-induced or toxic liver disease	ICD-11: DB95	Disease Info
Pathway Response	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hLCs (Liver cells)
In Vivo Model	Totally 128 7-week-old ICR male mice (22-25 g) were provided by Dashuo Biological Technology (Chengdu, China). The animals were divided into four groups (32 mice per group) randomly. The mice in the three experimental groups were gavage administered with Ni (NiCl2·6H2O) at doses of 7.5, 15, and 30 mg/kg body weight respectively, while those in the control group were given distilled water. The Ni dose adopted here was determined according to the value of median lethal dose (LD50, 306.11 mg/kg) attained in the research on acute oral toxicity of male mice. We selected 1/40, 1/20 and 1/10 LD50 (306.11 mg/kg) of NiCl2 in this study. Click to Show/Hide
Response regulation	Nickel chloride caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice.

Ferritin heavy chain (FTH1)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target			[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Drug-induced or toxic liver disease	ICD-11: DB95	Disease Info
Pathway Response	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hLCs (Liver cells)
In Vivo Model	Totally 128 7-week-old ICR male mice (22-25 g) were provided by Dashuo Biological Technology (Chengdu, China). The animals were divided into four groups (32 mice per group) randomly. The mice in the three experimental groups were gavage administered with Ni (NiCl2·6H2O) at doses of 7.5, 15, and 30 mg/kg body weight respectively, while those in the control group were given distilled water. The Ni dose adopted here was determined according to the value of median lethal dose (LD50, 306.11 mg/kg) attained in the research on acute oral toxicity of male mice. We selected 1/40, 1/20 and 1/10 LD50 (306.11 mg/kg) of NiCl2 in this study. Click to Show/Hide
Response regulation	Nickel chloride caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice.

References

Ref 1	Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice. Toxicology. 2022 Jan 30;466:153068. doi: 10.1016/j.tox.2021.153068. Epub 2021 Dec 16.