Evaluation the binding of chelerythrine, a potentially harmful toxin, with bovine serum albumin

Shen, Yizhong; Zhu, Chao; Wang, Yaping; Xu, Jingjing; Xue, Ruyu; Ji, Fuyun; Wu, Yiwei; Wu, Zeyu; Zhang, Wencheng; Zheng, Zhi; Ye, Yingwang

doi:10.1016/j.fct.2019.110933

Cited by 20 publications

(12 citation statements)

References 37 publications

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“…Specifically, we identified significantly higher levels of the ALI–protein adduct in serum after 24 h of AAI administration, with the highest being detected at ∼300 adducts per 10 9 amino acids. The huge drop in albumin adduct levels from day 1 to day 2 postdosing could be related to the transport function of albumin, as albumin was reported to deliver various substances including drug and ultimate carcinogenic/toxic metabolites around the human bodies. , This was also supported by the maximum ALI–protein adduct levels detected in tissues on day 2 postdosing (Figure ).…”

Section: Resultsmentioning

confidence: 80%

“…The huge drop in albumin adduct levels from day 1 to day 2 postdosing could be related to the transport function of albumin, as albumin was reported to deliver various substances including drug and ultimate carcinogenic/toxic metabolites around the human bodies. 54,55 This was also supported by the maximum ALI−protein adduct levels detected in tissues on day 2 postdosing (Figure 5).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Quantitation of Protein Adducts of Aristolochic Acid I by Liquid Chromatography–Tandem Mass Spectrometry: A Novel Method for Biomonitoring Aristolochic Acid Exposure

Chan

Liu

et al. 2021

Chem. Res. Toxicol.

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Emerging evidence suggests that chronic exposure to aristolochic acids (AAs) is one of the etiological pathways leading to chronic kidney disease (CKD). Due to the traditional practice of herbal medicine and AA-containing plants being used extensively as medicinal herbs, over 100 million East Asians are estimated to be at risk of AA poisoning. Given that the chronic nephrotoxicity of AAs only manifests itself after decades of exposure, early diagnosis of AA exposure could allow for timely intervention and disease risk reduction. However, an early detection method is not yet available, and diagnosis can only be established at the end stage of CKD. The goal of this study was to develop a highly sensitive and selective method to quantitate protein adducts of aristolochic acid I (AAI) as a biomarker of AA exposure. The method entails the release of protein-bound aristolactam I (ALI) by heat-assisted alkaline hydrolysis, extraction of ALI, addition of internal standard, and quantitation by liquid chromatography–tandem mass spectrometric analysis. Accuracy and precision of the method were critically evaluated using a synthetic ALI-containing glutathione adduct. The validated method was subsequently used to detect dose-dependent formation of ALI–protein adducts in human serum albumin exposed to AAI and in proteins isolated from the tissues and sera of AAI-exposed rats. Our time-dependent study showed that ALI–protein adducts remained detectable in rats even at 28 days postdosing. It is anticipated that the developed method will fill the technical gap in diagnosing AA intoxication and facilitate the biomonitoring of human exposures to AAs.

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Section: Resultsmentioning

confidence: 80%

Section: ■ Results and Discussionmentioning

confidence: 99%

Quantitation of Protein Adducts of Aristolochic Acid I by Liquid Chromatography–Tandem Mass Spectrometry: A Novel Method for Biomonitoring Aristolochic Acid Exposure

Chan

Liu

et al. 2021

Chem. Res. Toxicol.

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“…Forster resonance energy transfer (FRET) is a valuable and widely used tool to compute the energy transfer efficacy from donor to acceptor molecules and to measure the distance between ligands and fluorophores in serum albumin in an aqueous environment. 50 The FRET principle states that the energy transfer between a donor and an acceptor is well-achieved when both are situated at a distance between 2 and 8 nm, the donor molecule is fluorescent, and overlapping is significant between the donor emission spectrum and the acceptor absorbance spectrum. 51 The efficiency of energy transfer was calculated with the help of eq 2 where R 0 6 is the critical distance between the donor and the acceptor when the energy transfer efficiency is equal to 50% and r 6 represents the distance between the donor and the acceptor.…”

Section: Resultsmentioning

confidence: 99%

“…Förster resonance energy transfer (FRET) is a valuable and widely used tool to compute the energy transfer efficacy from donor to acceptor molecules and to measure the distance between ligands and fluorophores in serum albumin in an aqueous environment . The FRET principle states that the energy transfer between a donor and an acceptor is well-achieved when both are situated at a distance between 2 and 8 nm, the donor molecule is fluorescent, and overlapping is significant between the donor emission spectrum and the acceptor absorbance spectrum .…”

Section: Resultsmentioning

confidence: 99%

Aflatoxin B₁ Induced Structural and Conformational Changes in Bovine Serum Albumin: A Multispectroscopic and Circular Dichroism-Based Study

Qureshi

Javed

2021

ACS Omega

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Aflatoxin B 1 (AFB 1 ) is a mutagen that has been categorized as a group 1 human carcinogen by the International Agency for Research on Cancer. It is produced as a secondary metabolite by soil fungi Aspergillus flavus and Aspergillus parasiticus. Here, in this study, the effect of AFB 1 on the structure and conformation of bovine serum albumin (BSA) using multispectroscopic tools like fluorescence spectroscopy, ultraviolet−visible absorption spectroscopy, and circular dichroism spectropolarimetry has been ascertained. Ultraviolet absorption spectroscopy revealed hyperchromicity in the absorption spectra of BSA in the presence of AFB 1 . The binding constant was calculated in the range of 10 4 M −1 , by fluorescence spectroscopy suggesting moderate binding of the toxin to BSA. The study also confirms the static nature of fluorescence quenching. The stoichiometry of binding sites was found to be unity. The competing capability of warfarin for AFB 1 was higher than ibuprofen as calculated from site marker displacement assay. Forster resonance energy transfer confirmed the high efficiency of energy transfer from BSA to AFB 1 . Circular dichroism spectropolarimetry showed a decrease in the α-helix in BSA in the presence of AFB 1 . The melting temperature of BSA underwent an increment in the presence of a mycotoxin from 62.5 to 70.3 °C. Molecular docking confirmed the binding of AFB 1 to subdomain IIA in BSA. ■ HIGHLIGHTS• In this study, binding dynamics of AFB 1 with BSA were explored by UV absorption spectroscopy, fluorescence spectroscopy, and molecular docking.• Molecular docking analysis substantiated that Arg-217, Tyr-149, Arg-256, and Ala-260 residues stabilize the interacting complex via hydrogen bonding.

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“…Chelerythrine (CHE), sanguinarine, and coptisine have been identified as the main hepatotoxic components of Chelidonium majus L. [ 14 ]. Notably, CHE is a benzophenanthridine alkaloid compound and has potent toxic effects via several in vivo and in vitro studies [ 15 ]. CHE is a natural inhibitor of the protein kinase C (PKC) isoenzyme, which is a critical regulator in controlling cell proliferation, differentiation, growth, and survival [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

et al. 2022

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Chelerythrine (CHE) is a majorly harmful isoquinoline alkaloid ingredient in Chelidonium majus that could trigger potential hepatotoxicity, but the pivotal molecular mechanisms remain largely unknown. In the present study, CHE-induced cytotoxicity and the underlying toxic mechanisms were investigated using human HepG2 cells in vitro. Data showed that CHE treatment (at 1.25–10 μM)-induced cytotoxicity in HepG2 cells is dose-dependent. CHE treatment increased the production of ROS and induced oxidative stress in HepG2 cells. Additionally, CHE treatment triggered the loss of mitochondrial membrane potential, decreased the expression of mitochondrial complexes, upregulated the expression of Bax, CytC, and cleaved-PARP1 proteins and the activities of caspase-9 and caspase-3, and downregulated the expression of Bcl-XL, and HO-1 proteins, finally resulting in cell apoptosis. N-acetylcysteine supplementation significantly inhibited CHE-induced ROS production and apoptosis. Furthermore, CHE treatment significantly downregulated the expression of phosphorylation (p)-Akt (Ser473), p-mTOR (Ser2448), and p-AMPK (Thr172) proteins in HepG2 cells. Pharmacology inhibition of Akt promoted CHE-induced the downregulation of HO-1 protein, caspase activation, and apoptosis. In conclusion, CHE-induced cytotoxicity may involve the inhibition of Akt pathway and the activation of oxidative stress-mediated mitochondrial apoptotic pathway in HepG2 cells. This study sheds new insights into understanding the toxic mechanisms and health risks of CHE.

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Evaluation the binding of chelerythrine, a potentially harmful toxin, with bovine serum albumin

Cited by 20 publications

References 37 publications

Quantitation of Protein Adducts of Aristolochic Acid I by Liquid Chromatography–Tandem Mass Spectrometry: A Novel Method for Biomonitoring Aristolochic Acid Exposure

Quantitation of Protein Adducts of Aristolochic Acid I by Liquid Chromatography–Tandem Mass Spectrometry: A Novel Method for Biomonitoring Aristolochic Acid Exposure

Aflatoxin B₁ Induced Structural and Conformational Changes in Bovine Serum Albumin: A Multispectroscopic and Circular Dichroism-Based Study

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

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Evaluation the binding of chelerythrine, a potentially harmful toxin, with bovine serum albumin

Cited by 20 publications

References 37 publications

Quantitation of Protein Adducts of Aristolochic Acid I by Liquid Chromatography–Tandem Mass Spectrometry: A Novel Method for Biomonitoring Aristolochic Acid Exposure

Quantitation of Protein Adducts of Aristolochic Acid I by Liquid Chromatography–Tandem Mass Spectrometry: A Novel Method for Biomonitoring Aristolochic Acid Exposure

Aflatoxin B1 Induced Structural and Conformational Changes in Bovine Serum Albumin: A Multispectroscopic and Circular Dichroism-Based Study

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

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Aflatoxin B₁ Induced Structural and Conformational Changes in Bovine Serum Albumin: A Multispectroscopic and Circular Dichroism-Based Study