Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00103)
Name |
Chronic obstructive pulmonary disease
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ICD |
ICD-11: CA22
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Full List of Target(s) of This Ferroptosis-centered Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
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 | Chronic obstructive pulmonary disease [ICD-11: CA22] | ||||
Responsed Drug | Dihydroquercetin | Preclinical | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HBE1 cells | Normal | Homo sapiens | CVCL_0287 | |
In Vivo Model |
Thirty-two male BALB/c mice (21-25 g, 6-8 weeks) were purchased from Hunan Slyke Jingda Laboratory Animal Co., Ltd. and kept in a clean unit at 23 ± 2 , 50% ± 10% relative humidity and 12 h rhythm of light and dark. Mice were randomly divided into four groups (n = 8 for each group): the control group, cigarette smoke-inducedCOPDgroup, COPD + low dose (50mg/kg/d)DHQgroup, and COPD + high dose (100 mg/kg/d) DHQ group. The mice in the control group were maintained in fresh air and given anintraperitoneal injectionof 0.3 ml/20 g phosphate-buffered saline (PBS) on Days 0, 11, and 23. The COPD mouse model was established as previously described. Mice in this group were exposed to cigarette smoke for 2 cycles per day (1 h per cycle), 6 days per week for 4 consecutive weeks in a sealed box with ventilation holes except for Days 0, 11, and 22, and over these 3 days, the mice were intraperitoneally injected with 0.3 ml/20g 100% CSE. Mice in the COPD+low-dose DHQ group and COPD+high-dose DHQ group were treated with cigarette smoke and 100% CSE as mentioned above and intraperitoneally injected with DHQ for 25 consecutive days except for Days 0, 11, and 22, while mice in the control and COPD groups were intraperitoneally injected with an equal volume of PBS except for Days 0, 11, and 22. All mice were sacrificed by intraperitoneal injection of 0.5 ml 3% chloral hydrateon the 29 th day of the experiment.
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Response regulation | Treatment with DHQ (Taxifolin) significantly reverses the ferroptosis induced by cigarette smoke both in vivo and in vitro via a Nrf2-dependent signaling pathway. These findings may provide novel therapeutic options for the treatment of chronic obstructive pulmonary disease (COPD) patients. | ||||
Unspecific Target
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Responsed Disease | Chronic obstructive pulmonary disease complicated with atherosclerosis [ICD-11: CA22] | ||||
Responsed Drug | Tongxinluo | Investigative | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hPMECs (Human pulmonary microvascular endothelial cells) | ||||
In Vivo Model |
The mice were randomly divided into the following six groups (n = 10 per group): the control (CON) group, which included C57BL/6 mice that were exposed to ambient air only, fed standard rodent chow (Beijing Keao Xieli Feed Co., Ltd., Beijing, China) and perfused with 0.5% carboxymethylcellulose (CMC) sodium solution; the high-fat diet (HFD) group, which included ApoEmice that were exposed to ambient air, fed a high-fat and high-cholesterol diet and perfused with 0.5% CMC sodium solution; the CS and HFD (CS+HFD) group, which included ApoEmice that were exposed to CS in a glass box, fed a HFD, and perfused with 0.5% CMC sodium solution; theATOgroup, which included ApoEmice (exposed to CS and HFD) that were perfused with 0.01 g/kg/day ATO calcium tablets; the TXL group, which included ApoEmice (exposed to CS and HFD) that were perfused with 0.75 g/kg/day TXL ultrafine powder; and the ATO/TXL combination therapy (ATO+TXL) group, which included ApoEmice (exposed to CS and HFD) that were perfused with a combination of 0.01 g/kg/day ATO and 0.75 g/kg/day TXL.
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Response regulation | Pulmonary microvascular barrier dysfunction plays an important role in chronic obstructive pulmonary disease complicated with atherosclerosis, and ferroptosis may be involved. Moreover, Tongxinluo (TXL) delays the progression of AS and reduces cardiovascular events by protecting the pulmonary microvascular barrier and inhibiting ferroptosis. | ||||
References