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

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 antitubercular drugs. 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 antitubercular 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 being 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 antitubercular drugs and significantly regulated the abundance of palmitoleic acid, 4-hydrobutyric acid, citrulline, gluconolactone, guanidinoacetic acid and piperidine acid in kidney.