Airway synthesis of 20-hydroxyeicosatetraenoic acid: metabolism by cyclooxygenase to a bronchodilator

1999 ◽  
Vol 276 (2) ◽  
pp. L280-L288 ◽  
Author(s):  
Elizabeth R. Jacobs ◽  
Richard M. Effros ◽  
John R. Falck ◽  
K. Malla Reddy ◽  
William B. Campbell ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Arachidonic Acid ◽  
Airway Resistance ◽  
Acid Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Dependent Manner ◽  
Hydroxyeicosatetraenoic Acid ◽  
Polar Metabolites ◽  
H 20

Rabbit airway tissue is a particularly rich source of cytochrome P-4504A protein, but very little information regarding the effect(s) of 20-hydroxyeicosatetraenoic acid (20-HETE) on bronchial tone is available. Our studies examined the response of rabbit bronchial rings to 20-HETE and the metabolism of arachidonic acid and 20-HETE from airway microsomes. 20-HETE (10−8 to 10−6 M) produced a concentration-dependent relaxation of bronchial rings precontracted with KCl or histamine but not with carbachol. Relaxation to 20-HETE was blocked by indomethacin or epithelium removal, consistent with the conversion of 20-HETE to a bronchial relaxant by epithelial cyclooxygenase. A cyclooxygenase product of 20-HETE also elicited relaxation of bronchial rings. [14C]arachidonic acid was converted by airway microsomes to products that comigrated with authentic 20-HETE (confirmed by gas chromatography-mass spectrometry as 19- and 20-HETE) and to unidentified polar metabolites. [3H]20-HETE was metabolized to indomethacin-inhibitable products. These data suggest that 20-HETE is an endogenous product of rabbit airway tissue and may modulate airway resistance in a cyclooxygenase-dependent manner.

scholarly journals Tetrahydropalmatine Poisoning: Diagnoses of Nine Adult Overdoses Based on Toxicology Screens by HPLC with Diode-Array Detection and Gas Chromatography–Mass Spectrometry

1999 ◽  
Vol 45 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Chi-Kong Lai ◽  
Albert Yan-Wo Chan
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Solid Phase ◽  
Gas Chromatography Mass Spectrometry ◽  
Diode Array ◽  
Diode Array Detection ◽  
Chromatography Mass Spectrometry ◽  
Polar Metabolites ◽  
Array Detection ◽  
Neurological Disturbance

Abstract Background: Tetrahydropalmatine (THP) is a neuroactive alkaloid with analgesic and hypnotic action. Its analysis is important because cases of human poisonings have emerged as a result of unregulated use of some proprietary biopharmaceuticals containing purified THP. Methods: We established analytical parameters for HPLC with diode-array detection (HPLC-DAD) and gas chromatography–mass spectrometry (GC-MS) for the detection of THP in serum and urine. Nine acutely THP-poisoned adults were thus screened over 16 months. Results: All patients recovered quickly after mild neurological disturbance. In general, THP was metabolized rapidly and excreted as polar metabolites in urine. Serum THP was measured in five cases and found to be <0.1–1.2 mg/L (<0.3–3.4 μmol/L). Paired analyses of urine with and without glucuronidase treatment clarified the disposition of THP. Our GC–MS method with trimethylsilane derivatization identified O-desmethyl metabolites. With a uniform solid-phase extraction, the HPLC-DAD procedure detected intact glucuronide metabolites. Conclusion: Intact glucuronide metabolites of THP are sensitive markers for THP exposures. Our methods and findings provide practical tools and information for surveillance of intoxication caused by excessive THP intake.

scholarly journals Measurement of 20-Hydroxyeicosatetraenoic Acid in Human Urine by Gas Chromatography–Mass Spectrometry

2004 ◽  
Vol 50 (1) ◽  
pp. 224-226 ◽  
Author(s):  
Jennifer Rivera ◽  
Natalie Ward ◽  
Jonathan Hodgson ◽  
Ian B Puddey ◽  
John R Falck ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Human Urine ◽  
Gas Chromatography Mass Spectrometry ◽  
Hydroxyeicosatetraenoic Acid ◽  
Chromatography Mass Spectrometry

scholarly journals Metabolomics Study with Gas Chromatography-Mass Spectrometry of Hepatotoxicity on Adult Zebrafish (Brachydanio Rerio) after Exposure to Diquat

2022 ◽  
Author(s):  
Ye Xiao ◽  
Xiang Lin ◽  
Zhong-Qun Liu ◽  
Mei-Lan Zhou ◽  
Tian-Yu Ren ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Amino Acid ◽  
Energy Metabolism ◽  
Freshwater Fish ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Brachydanio Rerio ◽  
Chromatography Mass Spectrometry

Abstract Although diquat is a widely used water-soluble herbicide in the world, its toxicity to freshwater fish has not been well characterized. In this study, gas chromatography-mass spectrometry (GC-MS) based metabolomics approach combined with histopathological examination and biochemical assays was applied to comprehensively assess the hepatotoxicity in zebrafish (Brachydanio rerio) after diquat exposure at two dosages of 0.34 and 1.69 mg·L−1 for 35 days. The results indicated that 1.69 mg·L−1 diquat exposure cause serious cellular swell and vacuolization with increased nuclear abnormality, and lead to obvious disturbance of antioxidative system and dysfunction in liver; while no obvious pathological injury could be detected, and changes in liver biochemistry were less pronounced at the dose level of 0.34 mg·L−1. Multivariate statistical analysis and pattern recognition showed different GC-MS profiles of zebrafish liver following exposure to diquat, the cluster of the treated groups were both clearly separated from the control samples. The differentially abundant metabolites mainly include carbohydrates, amino acids, lipids, nucleotides, and their derivatives. In the exposure group of 1.69 mg·L−1 diquat, severe disturbances of amino acid metabolism played important biological roles associated with inhibition of energy metabolism, reduced immunity, and disorders in neurotransmitters as pathway analysis revealed. Additionally, fluctuation of inositol, creatine, and pantothenic acid, substances associated with stress regulation and signal transduction, participating in metabolic abnormalities in zebrafish with diquat-triggered hepatic damage. Energy metabolism of zebrafish exposed on 0.34 mg·L−1 diquat more inclined to rely on anaerobic glycolysis than the normal ones. Amino acid metabolism responses were less affected, but obvious interference effects on lipid metabolism were observed with 0.34 mg·L−1 diquat exposure. These results imply increased sensitivity of metabolomics versus histopathology and clinical chemistry in recognizing liver toxicity of diquat. This study will contribute to explore possible mechanism of hepatic damages on nontarget freshwater fish induced by diquat and provide important basis for its environmental risk assessment.

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