Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00112)

Name	Drug-induced or toxic liver disease
ICD	ICD-11: DB95

Full List of Target(s) of This Ferroptosis-centered Disease

Prostaglandin G/H synthase 2 (PTGS2)

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target			[1]
Target for Ferroptosis	Marker
Responsed Disease	Ni-induced hepatotoxicity [ICD-11: DB95]
Responsed Drug	Nickel Chloride	Investigative	Drug 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 Disease Response by This Target			[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Ni-induced hepatotoxicity [ICD-11: DB95]
Responsed Drug	Nickel Chloride	Investigative	Drug 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 Disease Response by This Target			[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Ni-induced hepatotoxicity [ICD-11: DB95]
Responsed Drug	Nickel Chloride	Investigative	Drug 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.