<i>In Vitro</i> and <i>In Vivo</i> Evidence for RNA Adduction Resulting from Metabolic Activation of Methyleugenol

Yang, Xiaojing; Feng, Yanhui; Zhang, Zhengyu; Wang, Hui; Li, Weiwei; Wang, Dan Ohtan; Peng, Ying; Zheng, Jiang

doi:10.1021/acs.jafc.0c04880

Cited by 7 publications

(12 citation statements)

References 24 publications

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“…At later time points, the adduct levels moderately decreased, which may be attributable to DNA repair. In line with this notion, a recent study provided evidence for the involvement of DNA repair in the removal of E-3′-N2-dG adducts, albeit with limited efficiency [105]. Another explanation for the decreased adduct levels found at later time points could be cytotoxicity, which is indeed observed at high estragole concentrations [104].…”

Section: Dose-response Studies On the Genotoxic Potential Of Estragol...mentioning

confidence: 73%

Toxins in Botanical Drugs and Plant-derived Food and Feed – from Science to Regulation: A Workshop Review

Schrenk,

Allemang,

Fahrer

et al. 2024

Planta Med

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In September 2022, the 3rd International Workshop on pyrrolizidine alkaloids (PAs) and related phytotoxins was held on-line, entitled ʼToxins in botanical drugs and plant-derived food and feed – from science to regulationʼ. The workshop focused on new findings about the occurrence, exposure, toxicity, and risk assessment of PAs. In addition, new scientific results related to the risk assessment of alkenylbenzenes, a distinct class of herbal constituents, were presented. The presence of PAs and alkenylbenzenes in plant-derived food, feed, and herbal medicines has raised health concerns with respect to their acute and chronic toxicity but mainly related to the genotoxic and carcinogenic properties of several congeners. The compounds are natural constituents of a variety of plant families and species widely used in medicinal, food, and feed products. Their individual occurrence, levels, and toxic properties, together with the broad range of congeners present in nature, represent a striking challenge to modern toxicology. This review tries to provide an overview of the current knowledge on these compounds and indicates needs and perspectives for future research.

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Section: Dose-response Studies On the Genotoxic Potential Of Estragol...mentioning

confidence: 73%

Toxins in Botanical Drugs and Plant-derived Food and Feed – from Science to Regulation: A Workshop Review

Schrenk,

Allemang,

Fahrer

et al. 2024

Planta Med

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“…Beside this, Yang et al recently showed that reactive metabolites of methyleugenol were also able to form RNA adducts [118]. However, the biological consequences of these RNA adductions are so far unclear, as also mentioned by the authors.…”

Section: Genotoxicity Of Methyleugenol Vs Elemicinmentioning

confidence: 87%

Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food

Götz

Sachse

Schäfer

et al. 2022

Foods

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Alkenylbenzenes represent a group of naturally occurring substances that are synthesized as secondary metabolites in various plants, including nutmeg and basil. Many of the alkenylbenzene-containing plants are common spice plants and preparations thereof are used for flavoring purposes. However, many alkenylbenzenes are known toxicants. For example, safrole and methyleugenol were classified as genotoxic carcinogens based on extensive toxicological evidence. In contrast, reliable toxicological data, in particular regarding genotoxicity, carcinogenicity, and reproductive toxicity is missing for several other structurally closely related alkenylbenzenes, such as myristicin and elemicin. Moreover, existing data on the occurrence of these substances in various foods suffer from several limitations. Together, the existing data gaps regarding exposure and toxicity cause difficulty in evaluating health risks for humans. This review gives an overview on available occurrence data of myristicin, elemicin, and other selected alkenylbenzenes in certain foods. Moreover, the current knowledge on the toxicity of myristicin and elemicin in comparison to their structurally related and well-characterized derivatives safrole and methyleugenol, especially with respect to their genotoxic and carcinogenic potential, is discussed. Finally, this article focuses on existing data gaps regarding exposure and toxicity currently impeding the evaluation of adverse health effects potentially caused by myristicin and elemicin.

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“…The spontaneous departure of sulfate anion results in the formation of the corresponding benzylic cations (S N 1 reaction). The resultant electrophilic species react with nucleophilic sites of biological macromolecules such as DNA, and the biomolecule adduction disturbs the corresponding biological functions, leading to genotoxicity. ,− 1′-Hydroxy metabolite of MYR (M5, Scheme ) was reported to be more cytotoxic than MYR itself . The reactive metabolites of methyleugenol and safrole interact covalently with RNA previously. , With reactive metabolites of MYR, we evaluated the risk of RNA adduction.…”

Section: Discussionmentioning

confidence: 99%

RNA Adduction Resulting from the Metabolic Activation of Myristicin by P450 Enzymes and Sulfotransferases

He,

Cheng,

Zhang

et al. 2024

J. Agric. Food Chem.

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Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1′-hydroxyl and 3′-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by S N 1 and/or S N 2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.

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In Vitro and In Vivo Evidence for RNA Adduction Resulting from Metabolic Activation of Methyleugenol

Cited by 7 publications

References 24 publications

Toxins in Botanical Drugs and Plant-derived Food and Feed – from Science to Regulation: A Workshop Review

Toxins in Botanical Drugs and Plant-derived Food and Feed – from Science to Regulation: A Workshop Review

Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food

RNA Adduction Resulting from the Metabolic Activation of Myristicin by P450 Enzymes and Sulfotransferases

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