Protective effects of puerarin against tetrabromobisphenol a‐induced apoptosis and cardiac developmental toxicity in zebrafish embryo‐larvae

Abstract

Tetrabromobisphenol A (TBBPA), a brominated flame retardant, is detected commonly in aquatic environments, where it is thought to be highly toxic to the development of aquatic life. In this study, zebrafish embryos and larvae were used to investigate the protective effects of puerarin after exposure to TBBPA. Malformation, blood flow disorders, pericardial edema, and spawn coagulation rates increased, whereas survival decreased significantly after exposure to 0.5 and 1.0 mg L(-1) TBBPA. The measured indices of morphological toxicity improved after treatment with puerarin. TBBPA also induced reactive oxygen species (ROS) production in a dose-dependent manner. Acridine orange staining results revealed that TBBPA exposure caused cardiomyocyte apoptosis and induced the expression of three proapoptotic genes: P53, Bax, and Caspase9. In contrast, the expression of the antiapoptotic gene Bcl2 was down-regulated. When genes related to cardiac development were assessed, the expression of Tbx1, Raldh2, and Bmp2b changed after exposure to the combination of TBBPA and puerarin. These results suggest that TBBPA induces cardiomyocyte apoptosis and ROS production, resulting in cardiac developmental toxicity in zebrafish embryos or larvae. Therefore, puerarin regulates the expression of cardiac developmental genes, such as Tbx1, Bmp2b, and Raldh2 by inhibiting ROS production, and subsequently modulates cardiac development after the exposure of zebrafish larvae to TBBPA.

Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

“…There are conflicting reports on whether TBBPA has estrogenic activity in larval zebrafish with one group (Chow et al, 2013) reporting increased vitellogenin (an estrogenic biomarker in zebrafish) expression at high TBBPA concentrations, but another group reporting no estrogenic activity (Song et al, 2014). Many different laboratories (Kalasekar et al, 2014; McCormick et al, 2010; Noyes et al, 2015; Song et al, 2014; Yang et al, 2014) have reported that TBBPA produces malformations and lethality in developing zebrafish in the low micromolar ranges in agreement with our reported POD of 4.6 µM (Table 3). We did not observe changes in behavior after developmental exposure, but we did note marked changes in behavior after acute exposure, which correlates with what has been reported in mammals: TBBPA is, at most, a weak developmental neurotoxicant in mammals (Cope et al, 2015; Eriksson et al, 2001; Lilienthal et al, 2008), but it does appear to produce extensive behavioral changes after an acute exposure in mice (Nakajima et al, 2009).…”

The Neuroprotective Effect of Puerarin in Acute Spinal Cord Injury Rats

“…Decreased number of TUNEL-positive cells evidenced the attenuated apoptosis in puerarin-treated rats. The anti-apoptotic effect of puerarin we observed here is consistent with previous studies which were focused on other diseases [41][42][43] and it may promote the recovery of rats from SCI.…”

Thyroid Hormone Disruptors Interfere with Molecular Pathways of Eye Development and Function in Zebrafish

“…For instance, thioredoxin (redox protein, antioxidant), glutaredoxin (redox enzyme), and protein disulfide isomerase (catalyzes protein folding) suggest that the treatment caused oxidative stress and tissue damage in the eye, which was antagonized by those redox and repair proteins. For both THDCs, induction of oxidative stress and reactive oxygen species formation in fish and rodents has been described before [44,45].…”