Mequindox induces apoptosis, DNA damage, and carcinogenicity in Wistar rats

Liu, Qianying; Lei, Zhixin; Gu, Changqin; Guo, Jingchao; Yu, Huiru; Fatima, Zainab; Zhou, Kaixiang; Shabbir, Muhammad Abu Bakr; Maan, Muhammad Kashif; Wu, Qinghua; Xie, Shuyu; Wang, Xu; Zhang, Yuan

doi:10.1016/j.fct.2019.03.025

Cited by 10 publications

(7 citation statements)

References 58 publications

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“…11 The major target tissues of MEQ are the hematological system, liver, kidneys, adrenal glands, and the developmental and reproductive systems. 44 Studies show that MEQ could induce reproductive toxicity and teratogenicity in rat maternal and embryonic populations. 45 Metabolites of MEQ exhibit toxicity that is more severe than that of the precursor.…”

Section: ■ Introductionmentioning

confidence: 99%

“…47 In another research, MEQ and its main metabolites M2 and M6 were reported with adrenal toxicity to H295R cells. 44 M2 was also reported to be the most potent metabolite of MEQ, exhibiting highest adrenal toxicity. 7 Reproductive toxicity has also been reported in association with M11 and M12.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Although MEQ exhibits lower toxicity than other drugs in the QdNOs family, toxicity studies about MEQ still show reproductive toxicity, carcinogenicity, mutagenicity, and adrenal cell toxicity . The major target tissues of MEQ are the hematological system, liver, kidneys, adrenal glands, and the developmental and reproductive systems . Studies show that MEQ could induce reproductive toxicity and teratogenicity in rat maternal and embryonic populations …”

Section: Introductionmentioning

confidence: 99%

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Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

An,

Li,

et al. 2024

Chem. Res. Toxicol.

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Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.

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Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

An,

Li,

et al. 2024

Chem. Res. Toxicol.

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“…Quinoxalines (Qx) are chemically synthesized antibacterial drugs that have a strong inhibitory effect on both gram-positive and gram-negative bacteria [ 1 , 2 ]. Due to the broad antimicrobial spectrum and obvious growth-promoting effects, Qx are used in excessive amounts by farmers as feed additives to obtain more economic benefits [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Metabolite as a Hapten to Prepare Monoclonal Antibodies for Rapid Screening of Quinoxaline Drug Residues

Song

Luo

et al. 2022

Foods

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Quinoxalines (Qx) are chemically synthesized antibacterial drugs with strong antibacterial and growth-promoting effects. Qx is heavily abused by farmers, resulting in large residues in animal-derived foods, which pose a serious threat to human health. Desoxyquinoxalines (DQx), which have the highest residue levels, have been identified as the major toxicant and have become a new generation of residue markers. In this study, we prepared monoclonal antibodies (mAb) based on a new generation metabolite (desoxymequindox, DMEQ) and establish an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) for the rapid determination of Qx residues in food. The mAb exhibited high sensitivity with half maximal inhibitory concentration (IC50) and a linear range of 2.84 µg/L and 0.8–12.8 µg/L, respectively. Additionally, the cross-reactivity (CR) of the mAb showed that it recognized multiple DQx to varying levels. The limits of detection (LOD), limits of quantification (LOQ), and recoveries for the ic-ELISA assay of pork, swine liver, swine kidney, chicken, and chicken liver were 0.48–0.58 µg/kg, 0.61–0.90 µg/kg, and 73.7–107.8%, respectively, and the coefficients of variation (CV) were less than 11%. The results of the ic-ELISA showed a good correlation with LC–MS/MS in animal-derived foods. This suggests that this analytical method can be used for the rapid screening of QX residues.

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“…Deriving from the same family of QdNOs with a corresponding basic structure, MEQ has attracted increasing attention due to corresponding toxic risk, including induced apoptosis, carcinogenicity, DNA damage, etc. [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolism Profile of Mequindox in Sea Cucumbers In Vivo Using LC-HRMS

Mao

Zhou

et al. 2022

Antibiotics

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In this work, the metabolism behavior of mequindox (MEQ) in sea cucumber in vivo was investigated using LC-HRMS. In total, nine metabolites were detected and identified as well as the precursor in sea cucumber tissues. The metabolic pathways of MEQ in sea cucumber mainly include hydrogenation reduction, deoxidation, carboxylation, deacetylation, and combinations thereof. The most predominant metabolites of MEQ in sea cucumber are 2-iso-BDMEQ and 2-iso-1-DMEQ, with deoxidation and carbonyl reduction as major metabolic pathways. In particular, this work first reported 3-methyl-2-quinoxalinecarboxylic acid (MQCA) as a metabolite of MEQ, and carboxylation is a major metabolic pathway of MEQ in sea cucumber. This work revealed that the metabolism of MEQ in marine animals is different from that in land animals. The metabolism results in this work could facilitate the accurate risk assessment of MEQ in sea cucumber and related marine foods.

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Mequindox induces apoptosis, DNA damage, and carcinogenicity in Wistar rats

Cited by 10 publications

References 58 publications

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

A Novel Metabolite as a Hapten to Prepare Monoclonal Antibodies for Rapid Screening of Quinoxaline Drug Residues

Metabolism Profile of Mequindox in Sea Cucumbers In Vivo Using LC-HRMS

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