Project description:Perfluoroalkyl substances (PFAS) are a class of synthetic chemicals that are persistent in the environment. Due to concerns linked with longer chain PFAS, shorter chain chemicals were used as replacements, but developmental toxicity assessments of the shorter chain chemicals are limited. The aim of this study was to compare the developmental toxicity of three perfluoroalkyl acids (PFAAs): perfluorooctanoic acid (PFOA), composed of 8 carbon (C8), perfluorohexanoic acid (PFHxA, C6), and perfluorobutanoic acid (PFBA, C4) using the zebrafish (Danio rerio). LC50s at 120 hour post fertilization (hpf) were determined to assess the potency of each PFAA by exposing developing zebrafish (1-120 hpf) to a range of concentrations. In sublethal assessments, zebrafish were exposed to 0, 4, 40, or 400 parts per billion (ppb; µg/L) of the PFAAs throughout embryonic development (1-72 hpf). Effects of the embryonic exposure on locomotor activities was completed with the visual motor response test at 120 hpf. At 72 hpf, morphological changes including total body length, head length, and head width were assessed. Additionally, transcriptomic profiles of PFOA, PFHxA, and PFBA were determined at 72 hpf to compare altered molecular and disease pathways. The LC50 ranking was PFOA > PFHxA > PFBA, which followed trend as expected based on chain length. PFOA caused hyperactivity and PFBA hypoactivity, while PFHxA did not change behavior. PFOA, PFHxA, and PFBA caused morphological and transcriptomic alterations that were unique for each chemical and were concentration dependent. Cancer was a top enriched disease for PFOA, while FXR/RXR activation was a top canonical pathway in all PFBA exposures. Overall, an embryonic exposure to PFOA, PFHxA, or PFBA resulted in morphological alterations in zebrafish eleuthero-embryos; however, only PFOA and PFBA induced neurobehavioral alterations. The transcriptomic profile of each chemical was unique indicating different toxicity mechanisms and were aligned with human adverse health outcomes supporting predictive value.

Project description:BackgroundSutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few studies report on its toxicology and dosage in vivo. There is still room to better understand its cytotoxicity effects in animal systems.MethodsWe prepared two extracts, one with 80% (v/v) ethanol, and the other, with water. Both were studied to determine the maximum tolerable concentration when extracts were applied at 0 to 200 μg/ml to a Tuebingen zebrafish embryo line. The development of zebrafish embryos after 24 h post fertilization (hpf) was studied. A concentration range of 5 μg/ml to 50 μg/ml was then chosen to monitor the ontological development of cultured embryos. A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was used to study the differences of the two experimental extracts. Chemical variation between the extracts was illustrated using chemometrics.ResultsBoth extracts led to bleeding and pericardial cyst formation when applied at high concentrations to the zebrafish embryo culture. Chronic teratogenic toxicities, leading to pericardial edema, yolk sac swelling, and other abnormal developmental characteristics, were detected. The aqueous extracts of S. frutescens were less toxic to the larvae than the ethanol extracts, validating preference for aqueous preparations when used in traditional medicine. Chemical differences between the water extracts and alcoholic extracts were analysed using LC-MS/MS. A supervised metabolomics approach, targeting the sutherlandiosides and sutherlandins using orthogonal partial least squares-discriminant analysis (OPLS-DA), illustrated that sutherlandiosides were the main chemical features that can be used to distinguish between the two extracts, despite the extracts being highly similar in their chemical constituents.ConclusionThe water extract caused less cytotoxic and abnormal developmental effects compared to the ethanolic extract, and, this is likely due to differences in concentrations of extracted chemicals rather than the chemical profile per se. This study provides more evidence of cytotoxicity effects linked to S. frutescens using the zebrafish embryo bioassay as a study tool.

Dataset Information

Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System.

Publications

Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System.

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