{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002390","ANALYSIS_ID":"AN003895","VERSION":"1","CREATED_ON":"02-08-2024"},

"PROJECT":{"PROJECT_TITLE":"The metabolomic resetting effect of DMXAA in cisplatin-induced AKI","PROJECT_TYPE":"MS quantitative analysis","PROJECT_SUMMARY":"Cisplatin-induced nephrotoxicity is the main adverse effect of cisplatin-based chemotherapy, which highly limits the clinical use of cisplatin. DMXAA, a flavonoid derivative as a known agonist of STING, has been served as a promising antivascular agent. Although cGAS-STING activation has been demonstrated to mediate cisplatin-induced AKI, the role of DMXAA in this condition is unclear. Here, we defined an unexpected and critical role of DMXAA in improving renal function, ameliorating renal tubular injury and cell apoptosis, suppressing inflammation in cisplatin-induced AKI. Moreover, we confirmed that DMXAA combated AKI in a STING-independent manner evidenced by its protection against AKI in STING knockout mice. Due to the established role of metabolic disorders in AKI, which could contribute to the injury and kidney recovery, we performed metabolomics using renal tissues from cisplatin-induced AKI mice with or without DMXAA treatment. Strikingly, the date revealed that DMXAA improved the metabolic disorders in kidneys of AKI mice, especially restored the tryptophan metabolism.","INSTITUTE":"Children's Hospital of Nanjing Medical University","DEPARTMENT":"Department of Nephrology, State Key Laboratory of Reproductive Medicine,","LABORATORY":"Nanjing Key Lab of Pediatrics, Jiangsu Key Laboratory of Pediatrics","LAST_NAME":"Lu","FIRST_NAME":"Lingling","ADDRESS":"Guangzhou Road 72, Nanjing, Jiangsu, 210000, China","EMAIL":"lulingling89tara@163.com","PHONE":"0086-25-8311-7435","DOI":"http://dx.doi.org/10.21228/M81B0N"},

"STUDY":{"STUDY_TITLE":"The metabolomic resetting effect of DMXAA in cisplatin-induced injured mouse kidney","STUDY_SUMMARY":"A single injection of cisplatin was used to induce AKI in mice. To assess the effect of DMXAA, the mice were injected intraperitoneally with DMXAA or vehicle one hour before cisplatin injection, repeated every 24 hours. The mice were euthanized 72 hours after cisplatin injection, and renal tissues were collected for MS analysis.","INSTITUTE":"Children's Hospital of Nanjing Medical University","LAST_NAME":"Lu","FIRST_NAME":"Lingling","ADDRESS":"Guangzhou Road 72, Nanjing, Jiangsu, 210000, China","EMAIL":"lulingling89tara@163.com","PHONE":"0086-25-8311-7435","SUBMIT_DATE":"2022-12-05"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","GENOTYPE_STRAIN":"C57BL/6J, wild type","AGE_OR_AGE_RANGE":"8 weeks","GENDER":"Male"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"C_1",
"Factors":{"Treatment":"control"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_C_1.mzML","RAW_FILE_NAME":"neg_C_1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"C_2",
"Factors":{"Treatment":"control"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_C_2.mzML","RAW_FILE_NAME":"neg_C_2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"C_3",
"Factors":{"Treatment":"control"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_C_3.mzML","RAW_FILE_NAME":"neg_C_3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"C_4",
"Factors":{"Treatment":"control"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_C_4.mzML","RAW_FILE_NAME":"neg_C_4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"C_5",
"Factors":{"Treatment":"control"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_C_5.mzML","RAW_FILE_NAME":"neg_C_5.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"XP_1",
"Factors":{"Treatment":"DMXAA+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_XP_1.mzML","RAW_FILE_NAME":"neg_XP_1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"X_P_2",
"Factors":{"Treatment":"DMXAA+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_XP_2.mzML","RAW_FILE_NAME":"neg_XP_2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"X_P_3",
"Factors":{"Treatment":"DMXAA+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_XP_3.mzML","RAW_FILE_NAME":"neg_XP_3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"X_P_4",
"Factors":{"Treatment":"DMXAA+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_XP_4.mzML","RAW_FILE_NAME":"neg_XP_4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"X_P_5",
"Factors":{"Treatment":"DMXAA+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_XP_5.mzML","RAW_FILE_NAME":"neg_XP_5.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"P_1",
"Factors":{"Treatment":"vehicle+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_P_1.mzML","RAW_FILE_NAME":"neg_P_1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"P_2",
"Factors":{"Treatment":"vehicle+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_P_2.mzML","RAW_FILE_NAME":"neg_P_2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"P_3",
"Factors":{"Treatment":"vehicle+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_P_3.mzML","RAW_FILE_NAME":"neg_P_3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"P_4",
"Factors":{"Treatment":"vehicle+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_P_4.mzML","RAW_FILE_NAME":"neg_P_4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"P_5",
"Factors":{"Treatment":"vehicle+cisplatin"},
"Additional sample data":{"Genotype":"WT","Strain":"C57BL/6J","Age":"8 weeks","Sex":"male","RAW_FILE_NAME":"pos_P_5.mzML","RAW_FILE_NAME":"neg_P_5.mzML"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"The mice were euthanized 72 hours after cisplatin injection, and renal tissues were collected and frozen at -80℃.","SAMPLE_TYPE":"Kidney","STORAGE_CONDITIONS":"-80℃"},

"TREATMENT":{"TREATMENT_SUMMARY":"Wild type C57BL/6J mice were maintained under standard environmental conditions. A single injection of cisplatin (25 mg/kg, i.p.) was used to induce AKI. To assess the effect of DMXAA, the mice were injected with DMXAA (10 mg/kg, i.p.) or vehicle one hour before cisplatin injection, repeated every 24 hours. The mice were euthanized 72 hours after cisplatin injection, and renal tissues were collected and frozen at -80℃."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"The samples were taken from the refrigerator at -80℃ and placed on the prepared dry ice. 30mg samples were taken and 400µL of extract (methanol: acetonitrile =3:1, pre-cooled at -40℃) was added. After the tissue crushing instrument was broken, the samples were ultrasonic and stood at 4℃ for 2 hours. The samples were removed and centrifuged for 15min (12000 rpm, 4℃), then the same amount was taken and concentrated to dry in vacuum. Then 100µL 50% methanol aqueous solution (methanol: water =1:1, v/v) was added for resolution, vortexed for 3min (4℃, 2000rpm), sonicated for 5min, centrifuged for 15min (12000 rpm, 4℃), and the supernatant was taken for injection analysis."},

"CHROMATOGRAPHY":{"INSTRUMENT_NAME":"Thermo Vanquish liquid chromatograph.","COLUMN_NAME":"Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.7um)","CHROMATOGRAPHY_TYPE":"HILIC"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive HF-X Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"ESI","MS_COMMENTS":"Electrospray ionization (ESI) was used to detect positive and negative ions in each sample. The samples were separated by UHPLC and analyzed by mass spectrometry using a Thermo QE HF-X mass spectrometer. Analysis software: Xcalibur version 4.1.","ION_MODE":"NEGATIVE","MS_RESULTS_FILE":"ST002390_AN003895_Results.txt UNITS:Average normalized quantitative value Has m/z:Yes Has RT:Yes RT units:Minutes"}

}