Development and application of a comparative fatty acid analysis method to investigate voriconazole-induced hepatotoxicity

Chen, Guan-Yuan; Chiu, Huai-Hsuan; Lin, Shu-Wen; Tseng, Yufeng J.; Tsai, Sung-Jeng; Kuo, Ching‐Hua

doi:10.1016/j.cca.2014.08.013

Cited by 12 publications

(4 citation statements)

References 48 publications

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“…The chloroform layer was dissolved in N-hexane and KOH - methanol solvent (0.5 mol/l) with 4:1 volume ratio at 70 °C for 20 min, vibrated in the ultrasonic cleaner for 5 min, centrifuged at 3500× g for 10 min, and the fatty acids were collected from the N-hexane layer. Finally, quantitative fatty acid analysis was conducted by gas chromatography with mass spectrometric detection (GC-MS, Thermo Trace, Silicon Valley, USA) [ 24 ], with minor modifications. Briefly, the oven temperature was set to 40 °C for 1 min and then increased to 260 °C at a rate of 5 °C/min and holding for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Molecular and biochemical responses in the midgut of the silkworm, Bombyx mori, infected with Nosema bombycis

Wang

et al. 2018

Parasites Vectors

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BackgroundMicrosporidia are a group of eukaryotic intracellular parasites that infect almost all vertebrates and invertebrates. However, there is little information available of how microsporidia obtain nutrients and energy from host cells. The purpose of this study was to investigate the energy and material requirements of Nosema bombycis for the invasion procedure through analyzing the global variation of the gene expression, protein abundance, fatty acids level and ATP flux induced by the microsporidia N. bombycis infection in the midgut of the silkworm Bombyx mori.MethodsA suppression subtractive hybridization (SSH) and quantitative real-time PCR (qPCR) analysis were performed to identify the genes upregulated in the midgut of B. mori 48 h following N. bombycis infection. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to annotate and summarize the differentially expressed genes, according to the categories ‘molecular function’, ‘cellular component’ and ‘biological process’. To evaluate the nutrition material and energy costs in B.mori infected by N. bombycis, biochemical analysis was performed to determine the variation of protein abundance, fatty acid levels and ATP flux with or without the microsporidia N. bombycis infection in the midgut of the silkworm B. mori.ResultsA total of 744 clones were obtained, 288 clones were randomly selected for sequencing, and 110 unigenes were generated. Amongst these, 49.21%, 30.16% and 14.29% genes were involved in 19 molecular functions, 19 biological processes and nine cellular components, respectively. A total of 11 oxidative phosphorylation- and eight proton-coupled ATP synthesis-related genes were upregulated. Seven protein degradation-, three fat degradation-related genes were upregulated, and no genes related to the de novo synthesis of amino acids and fatty acids were significantly upregulated. The data from the biochemical analysis showed the contents of total protein and ATP of B. mori midgut tissues decreased significantly, whereas the fatty acid content did not significantly change after four days of N. bombycis infection. Microsporidia N. bombycis infection upregulated the expression level of genes involved in host ATP synthesis, protein and fat degradation, which eventually causes the obvious decline of protein content and ATP synthesis in the host midgut, whereas the fatty acids content did not change significantly.ConclusionsThis study suggested to some extent that N. bombycis invasion can activate the host protein degradation and accelerate the production of host ATP. Microsporidia of N. bombycis show preference for proteins rather than fatty acids from the host to ensure the material preparation required by their parasitic life-cycle. Requirements of N. bombycis for energy were also mainly dependent on the host ATP production. This study provides a new data that may help our understanding of the molecular mechanisms of obtaining energy and nutrients from the host by the microsporidium N. bombycis.Electronic su...

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Section: Methodsmentioning

confidence: 99%

Molecular and biochemical responses in the midgut of the silkworm, Bombyx mori, infected with Nosema bombycis

Wang

et al. 2018

Parasites Vectors

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“…The instrument was equipped with a capillary column (0.25 µm × 30 m × 0.25 mm, VF-WAXms; Agilent). Nonadecanoic acid (C19:0) (Sigma-Aldrich, St. Louis, MO, USA) was used as the internal standard for the following reasons: (1) it is chemically stable, (2) it elutes close to the fatty acids analyzed in this study, (3) it separates almost completely from all components in the sample, and (4) it is virtually absent in human blood [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Serum Fatty Acid Composition Balance by Fuzzy C-Means Method in Individuals with or without Metabolic Dysfunction-Associated Fatty Liver Disease

et al. 2023

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Circulating fatty acid composition is assumed to play an important role in metabolic dysfunction-associated fatty liver disease (MAFLD) pathogenesis. This study aimed to investigate the association between the overall balance of serum fatty acid composition and MAFLD prevalence. This cross-sectional study involved 400 Japanese individuals recruited from a health-screening program. We measured fatty acids in serum lipids using gas chromatography–mass spectrometry. The serum fatty acid composition balance was evaluated using fuzzy c-means clustering, which assigns individual data points to multiple clusters and calculates the percentage of data points belonging to multiple clusters, and serum fatty acid mass%. The participants were classified into four characteristic subclasses (i.e., Clusters 1, 2, 3, and 4), and the specific serum fatty acid composition balance (i.e., Cluster 4) was associated with a higher MAFLD prevalence. We suggest that the fuzzy c-means method can be used to determine the circulating fatty acid composition balance and highlight the importance of focusing on this balance when examining the relationship between MAFLD and serum fatty acids.

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“…A recently published method uses unlabeled or deuterated methanol, followed by GC-MS analysis in order to speed up the metabolic profiling of fatty acids, useful for establishing the presence and the mechanism of voriconazole induced liver toxicity, and the possibility to use fatty acids as markers of toxicity [14] . Frechen et al [15] developed a coupled dynamic model useful to study the interaction of voriconazole (a CYP3A inhibitor) and midazolam (a CYP3A substrate).…”

Section: Liver Toxicitymentioning

confidence: 99%

Voriconazole and the liver

Mihăilă

2015

WJH

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Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinear pharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 μg/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients.

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Development and application of a comparative fatty acid analysis method to investigate voriconazole-induced hepatotoxicity

Cited by 12 publications

References 48 publications

Molecular and biochemical responses in the midgut of the silkworm, Bombyx mori, infected with Nosema bombycis

Molecular and biochemical responses in the midgut of the silkworm, Bombyx mori, infected with Nosema bombycis

Serum Fatty Acid Composition Balance by Fuzzy C-Means Method in Individuals with or without Metabolic Dysfunction-Associated Fatty Liver Disease

Voriconazole and the liver

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