Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0392)

Name	Lipopolysaccharide
Drug Type	Others

Full List of Ferroptosis Target Related to This Drug

Unspecific Target

In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
Responsed Regulator	Mitogen-activated protein kinase kinase kinase 11 (MAP3K11)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
Response regulation	Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
Responsed Regulator	Cellular tumor antigen p53 (TP53)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
Response regulation	Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.

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				[2]
Target for Ferroptosis	Suppressor
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. Click to Show/Hide
Response regulation	The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues.

Cystine/glutamate transporter (SLC7A11)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[2]
Target for Ferroptosis	Suppressor
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. Click to Show/Hide
Response regulation	The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues.

References

Ref 1	Silence of MLK3 alleviates lipopolysaccharide-induced lung epithelial cell injury via inhibiting p53-mediated ferroptosis. J Mol Histol. 2022 Apr;53(2):503-510. doi: 10.1007/s10735-022-10064-y. Epub 2022 Mar 5.
Ref 2	Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis. Cell Mol Biol Lett. 2020 Feb 27;25:10. doi: 10.1186/s11658-020-00205-0. eCollection 2020.