GC‐MS‐based metabolomics reveals mechanism of action for hydrazine induced hepatotoxicity in rats

Abstract

Gas chromatography-mass spectrometry (GC-MS) has great advantages for analyzing organic/amino acids, which are often targets in efficacy and/or toxicity studies. Although GC-MS has been used for the detection of many metabolic disorders, applications of GC-MS-based metabolomics in pharmacology/toxicology are relatively underdeveloped. We intended to investigate applicability of a GC-MS-based metabolomics approach for toxicological evaluation, and tried to elucidate the mechanism of hydrazine-induced hepatotoxicity. Rats were administered hydrazine chloride orally (120 and 240 mg kg⁻¹), and urine, plasma and liver samples were collected at 24 or 48 h post-dosing. Conventional clinical chemistry and liver histopathology were performed, urine and plasma were analyzed by GC-MS, and metabolic profiles were assessed using chemometric techniques. Principal component analysis score plots showed clear separation of the groups, indicating dose-dependent toxicity and recovery. The mechanism of toxicity was investigated based on semi-quantification data of identified metabolites. Amino acid precursors of glutathione (cystein, glutamate and glycine) and a product of glutathione metabolism (5-oxoproline) were elevated dose-dependently, accompanied with elevation of ascorbate levels. In addition, intermediates of the TCA cycle were decreased, whereas participants of the urea cycle and other amino acids were increased. These alterations were associated with histopathological changes such as fatty degeneration and glycogen accumulation. Application of GC-MS-based metabolomics revealed that oxidative stress and GSH consumption play important roles in the etiology of hydrazine-induced hepatotoxicity, demonstrating that this approach is a useful tool in pharmacology and toxicology for screening, elucidating mode of action and biomarker discovery.

Dissipation and residue determination of fluopyram and tebuconazole residues in watermelon and soil by GC-MS

“…Dong and J. Hu [19][20][21].Additionally, no information is available on simultaneous determination of fluopyram and tebuconazole in watermelon and soil by GC-MS. In this paper, a method based on Quick Easy Cheap Effective Rugged and Safe (QuEChERS) multi-residue method [1,22,23] to analyse fluopyram and tebuconazole in watermelon and soil by GC-MS was established.…”

Separation Technique for the Determination of Highly Polar Metabolites in Biological Samples

“…Mammalian cells depend on the metabolism of glucose and glutamine for proliferation. The coupling of separation methods, such as CE [106], GC [107], RPLC [108], and HILIC [109], to MS has proven to be effective for the detection of large numbers of metabolites in complex mixtures.…”

Urinary metabonomics study of Wu-tou-tang and its co-decoction with Pinelliae Rhizoma in adjuvant-induced arthritis rats

“…The main subjects of metabonomics are low molecular weight metabolites (MW < 1000 Da) Da) and their related biofluids, such as urine, plasma, or saliva. Nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and other hyphenated technologies have been generally used for metabolomics studies [2][3][4]. Ultra-performance liquid chromatography (UPLC) coupled with MS, especially MS with high resolution and sensitivity, is popularly used in metabonomics [5].…”