Butylated hydroxytoluene induces hyperactivity and alters dopamine-related gene expression in larval zebrafish (Danio rerio)

Liang, Xuefang; Zhao, Yaqian; Liu, Wang; Li, Zhitong; Souders, Christopher L.; Martyniuk, Christopher J.

doi:10.1016/j.envpol.2019.113624

Cited by 28 publications

(18 citation statements)

References 52 publications

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“…Noteworthy, the pivotal role played by the detected residues is supported by experimental data available in the literature [44,45,67,100]. According to the results of this work, side effects of BHT, such as anxiety [10] and reduced heart beating activity [48], could be caused by modulation of 5-HT 2C , GABA-AR, NET and DAT, in the central nervous system. This hypothesis is also supported by ADME analysis indicating that BHT is able to cross the blood-brain barrier.…”

Section: Discussionsupporting

confidence: 74%

“…These results suggest that BHT could have an inhibitory activity toward NET and the other monoamine transporters (SERT and DAT), as shown for PFL [98,101]. However, it should be noted that in two previous works, BHT and PFL were responsible for the modulation of DAT and NET expression, implying that the activity of these two molecules could be the result of both a direct and an indirect effect on these neurotransmitter transporters [10,102].…”

Section: Netmentioning

confidence: 62%

“…Diverse adverse effects have been reported for BHA such as DNA repair failure, genotoxicity, oxidative stress, carcinogenicity, reproductive toxicities, and endocrine disrupting effects [6][7][8]. Although BHT toxicity is still controversial, side effects have been shown, including carcinogenicity [9,10]. The current legislation takes these risks into account indicating a maximum concentration threshold.…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, for example, BHT is present in a variety of consumer products including rubber, foodstuff, cosmetics, plastics, mineral oil and fuel additives, pharmaceuticals, animal food and printing inks [8,9]. Indeed, BHT can be detected in seas, rivers, lakes, sediments and organisms [10][11][12]. To date, only three studies have reported the occurrence of SPAs in human samples [8,13]; thus, very little is known about their true dietary intake.…”

Section: Introductionmentioning

confidence: 99%

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Computational Methods for the Identification of Molecular Targets of Toxic Food Additives. Butylated Hydroxytoluene as a Case Study

et al. 2020

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Butylated hydroxytoluene (BHT) is one of the most commonly used synthetic antioxidants in food, cosmetic, pharmaceutical and petrochemical products. BHT is considered safe for human health; however, its widespread use together with the potential toxicological effects have increased consumers concern about the use of this synthetic food additive. In addition, the estimated daily intake of BHT has been demonstrated to exceed the recommended acceptable threshold. In the present work, using BHT as a case study, the usefulness of computational techniques, such as reverse screening and molecular docking, in identifying protein–ligand interactions of food additives at the bases of their toxicological effects has been probed. The computational methods here employed have been useful for the identification of several potential unknown targets of BHT, suggesting a possible explanation for its toxic effects. In silico analyses can be employed to identify new macromolecular targets of synthetic food additives and to explore their functional mechanisms or side effects. Noteworthy, this could be important for the cases in which there is an evident lack of experimental studies, as is the case for BHT.

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Section: Discussionsupporting

confidence: 74%

Section: Netmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Computational Methods for the Identification of Molecular Targets of Toxic Food Additives. Butylated Hydroxytoluene as a Case Study

et al. 2020

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“…The free radical-mediated hepatotoxicity can be effectively managed by the administration of agents that possess antioxidant, free radical scavenging, and anti-lipid peroxidation activities 6 . Search for completely effective and safe alternative drugs for the treatment of liver diseases is crucial because many of synthetic antioxidants currently in use for the purpose have been reported to have various side effects 7 . Macro-fungi, especially mushrooms, have been traditionally used in China and Japan to treat a variety of diseases for many years.…”

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confidence: 99%

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2020

IJPSR

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Even though numerous herbal preparations have been recommended in alternative systems of medicine against hepatic disorders, many of them cause severe toxicity upon prolonged use. Volvariella volvacea (Bull.: Fr.) Singer is a highly nutritious mushroom that can be incorporated into the regular diet without the fear of side effects. The protective effect of the aqueous ethanol extract of V. volvacea mycelia was evaluated against acetaminophen (APAP) induced hepatic damage in Wistar rats. A single dose of APAP (3 g/kg, p.o.) was used for inducing hepatic damage. The extract was administrated orally at doses of 250 and 500 mg/kg, once daily for 7 days. Treatment with APAP (3 g/kg) increased the activities of liver function enzymes serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP). APAP also reduced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and enhanced lipid peroxidation in liver tissue. Administration of V. volvacea extract (500 mg/kg, p.o.) decreased the activities of SGPT, SGOT, and ALP. It also enhanced the level of SOD, CAT as well as GPx and decreased the tissue MDA level. The results of the study revealed the protective effect of V. volvacea against APAP-induced hepatotoxicity. The activity is mediated through its antioxidant potential by scavenging the free radicals and also by maintaining the levels of hepatic antioxidant systems.

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Enantioselective toxic effects of mefentrifluconazole in the early life stage of zebrafish (Danio rerio)

Ren

Zhao

et al. 2022

Environmental Toxicology

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The research on the enantioselective toxic effects of chiral pesticides on non‐target aquatic organisms has attracted more and more attention. This study investigated the enantioselective toxic effects of mefentrifluconazole (MFZ) on acute toxicity, developmental toxicity, locomotor behaviors, and the mRNA relative expression levels of genes related to neurodevelopment and cardiac development in zebrafish embryos or larvae. The 96‐h lethal concentration 50 (LC50) values (exposed to racemate and enantiomers of MFZ, that is, rac‐MFZ/(−)‐MFZ/(+)‐MFZ) were 1.010, 1.552, and 0.753 mg/L for embryo, and 0.753, 1.187, and 0.553 mg/L for larvae. The rac‐MFZ/(−)‐MFZ/(+)‐MFZ can affect the heart development of zebrafish embryos, accompanied by heart rate inhibition, yolk sac deformities, pericardial deformities, and down‐regulation of genes related to cardiotoxicity in larvae in an enantioselective manner. Moreover, the rac‐MFZ/(−)‐MFZ/(+)‐MFZ also can affect the neural development of zebrafish embryos, accompanied by autonomic movement inhibition, swimming speed and swimming distance abnormalities, and down‐regulation of genes related to neurotoxicity in larvae in an enantioselective manner. For all toxicity endpoints, the effect of the (+)‐MFZ to early‐staged zebrafish were significantly greater than that of (−)‐MFZ. These results will help distinguishing the difference of MFZ enantiomers to zebrafish, and provide scientific reference for improving the risk assessment of chiral pesticides MFZ.

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Butylated hydroxytoluene induces hyperactivity and alters dopamine-related gene expression in larval zebrafish (Danio rerio)

Cited by 28 publications

References 52 publications

Computational Methods for the Identification of Molecular Targets of Toxic Food Additives. Butylated Hydroxytoluene as a Case Study

Computational Methods for the Identification of Molecular Targets of Toxic Food Additives. Butylated Hydroxytoluene as a Case Study

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Enantioselective toxic effects of mefentrifluconazole in the early life stage of zebrafish (Danio rerio)

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