Article 2021 · 36 citations

An approach to evaluating the potential teratogenic and neurotoxic mechanism of BHA based on apoptosis induced by oxidative stress in zebrafish embryo (<i>Danio rerio</i>)

Baran, A., Yildirim, S., Ghosigharehaghaji, A., Bolat, I, Sulukan, E., Ceyhun, S. B.

Abstract

Butylated hydroxyanisole (BHA) has been widely used in the cosmetics, pharmaceutical, and food industries due to its antioxidant activity. Despite the antioxidant effects, reported adverse effects of BHA at the cellular level have made its use controversial. In this regard, this study was performed to elucidate the potential toxicity mechanism caused by BHA at the molecular level in zebrafish embryos. For this purpose, zebrafish embryos were exposed to BHA at levels of 0.5, 1, 5, 7.5 and 10 ppm and monitored at 24, 48, 72 and 96 hours. Survival rate, hatching rate and malformations were evaluated. We examined the potential for reactive oxygen species (ROS) production and apoptosis signalling accumulation in the whole body. Moreover, we evaluated histopathological and immunohistochemical (8-OHDG) characterization of the brain in zebrafish embryos at the 96th hour. We also examined apoptosis, histopathological and immunohistochemical (8-OHDG) characteristics in 96 hpf zebrafish larvae exposed to tertiary butylhydroquinone (TBHQ), one of the major metabolites of BHA, at doses of 0.5, 2.5, 3.75 and 5 ppm. Consequently, it has been considered that increased embryonic and larval malformations in this study may have been caused by ROS-induced apoptosis. After 96 h of exposure, positive 8-OHdG immunofluorescence, degenerative changes, and necrosis were observed in the brain of BHA and TBHQ-treated zebrafish larvae in a dose-dependent manner. BHA and TBHQ exposure could lead to an increase in 8-OHdG activities by resulting oxidative DNA damage. In particular, the obtained data indicate that the induction of ROS formation, occurring during exposure to BHA and/or multiple hydroxyl groups, could be responsible for apoptosis.

Keywords

Butylated hydroxyanisole BHA 8-OHdG food additive BUTYLATED HYDROXYANISOLE DNA-DAMAGE TERT-BUTYLHYDROQUINONE DEVELOPMENTAL TOXICITY MEDIATED MECHANISMS FREE-RADICALS FOOD ANTIOXIDANTS ROS CARCINOGENESIS

WoS Categories

Toxicology

Sustainable Development Goals

Good Health and Well-being Sustainable Cities and Communities

Citation

Journal: HUMAN & EXPERIMENTAL TOXICOLOGY
Year: 2021
Volume: 40
Issue: 3
Pages: 425-438
ISSN: 0960-3271
eISSN: 1477-0903
DOI: 10.1177/0960327120952140
WoS UID: WOS:000569059200001

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