Citation: PENG Lin-Xiu, XIE Tong, SHAN Jin-Jun. Metabolomic Study of Kidney Injury Induced by Antitubercular Drugs and Therapeutic Effect of Glutathione Based on Gas Chromatography-Mass Spectrometry[J]. Chinese Journal of Analytical Chemistry, ;2020, 48(9): 1160-1168. doi: 10.19756/j.issn.0253-3820.191579 shu

Metabolomic Study of Kidney Injury Induced by Antitubercular Drugs and Therapeutic Effect of Glutathione Based on Gas Chromatography-Mass Spectrometry

PENG Lin-Xiu ^1,2, ,
XIE Tong ^1,2,3 ,
SHAN Jin-Jun ^1,2,3

1.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China;
2.
Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China;
3.
Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing 210023, China

Received Date: 29 October 2019
Revised Date: 12 May 2020

Fund Project: This work was supported by the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica (No. JKLPSE201505) and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Histopathology and serum biochemical indicators (urea nitrogen and creatinine) were investigated to evaluate the kidney injury caused by the combination use of isoniazid (100 mg/kg/d, ig)) and rifampicin (100 mg/(kg·d, ig)), which were used as anti-tuberculous drug. The endogenous metabolites extracted from kidney tissue were evaluated based on gas chromatography-mass spectrometry coupled with partial least squares-discriminant analysis and other multidimensional as well as unidimensional statistical methods. Glutathione, which was reported to protect tissue from damage caused by anti-tuberculosis drugs, was used to treat rats(250 mg/(kg·d, iv)) with kidney damage. Biochemical indicators showed that creatinine and urea nitrogen increased (p<0.05) greatly after intragastrically administrated with isoniazid and rifampicin. In kidney, 31 endogenous metabolites were identified as potential biomarkers, including tyrosine, proline, uridine and palmitoleic acid, etc. All these results suggested that the combination use of isoniazid and rifampicin caused serious damage to kidney and disturbed the fatty acid metabolism, arginine and proline metabolism. In addition, glutathione reduced the level of serum urea nitrogen (p<0.05) obviously and alleviated proliferation of glomerular mesangium. These results indicated that glutathione had good therapeutic effects on kidney injury caused by antituberculous drug and significantly regulated the abundance of palmitoleic acid, 4-hydrobutyric acid, citrulline, gluconolactone, guanidinoacetic acid and piperidine acid in kidney.
- Antitubercular drugs,
- Kidney injury,
- Glutathione,
- Metabolomics,
- Gas chromatography-mass spectrometry
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