In vitro and in vivo acute toxicity of an artificial butter flavoring.

Flavorings used in cookies, electronic cigarettes, popcorn, and breads contain approximately 30 chemical compounds, which makes it difficult to determine and correlate signs and symptoms of acute, subacute or chronic toxicity. The aim of this study was to characterize a butter flavoring chemically and subsequently examine the in vitro and in vivo toxicological profile using cellular techniques, invertebrates, and lab mammals. For the first time, the ethyl butanoate was found as the main compound of a butter flavoring (97.75%) and 24 h-toxicity assay employing Artemia salina larvae revealed a linear effect and LC50 value of 14.7 (13.7-15.7) mg/ml (R2 = 0.9448). Previous reports about higher oral doses of ethyl butanoate were not found. Observational screening with doses between 150-1000 mg/kg by gavage displayed increased amount of defecation, palpebral ptosis, and grip strength reduction, predominantly at higher doses. The flavoring also produced clinical signs of toxicity and diazepam-like behavioral changes in mice, including loss of motor coordination, muscle relaxation, increase of locomotor activity and intestinal motility, and induction of diarrhea, with deaths occurring after 48 h exposure. This substance fits into category 3 of the Globally Harmonized System. Data demonstrated that butter flavoring altered the emotional state in Swiss mice and disrupted intestinal motility, which may be a result of neurochemical changes or direct lesions in the central/peripheral nervous systems.

Laboratory and physiological aspects of substitute metazoan models for in vivo pharmacotoxicological analysis.

New methods are essential to characterize the performance of substitute procedures for detecting therapeutic action(s) of a chemical or key signal of toxicological events. Herein, it was discussed the applications and advantages of using arthropods, worms, and fishes in pharmacological and/or toxicology assessments. First of all, the illusion of similarity covers many differences between humans and mice, remarkably about liver injury and metabolism of xenobiotics. Using invertebrates, especially earthworms (Eisenia fetida), brine shrimps (Artemia salina, Daphnia magna), and insects (Drosophila melanogaster) and vertebrates as small fishes (Oryzias latipes, Pimephales promelas, Danio rerio) has countless advantages, including fewer ethical conflicts, short life cycle, high reproduction rate, simpler to handle, and less complex anatomy. They can be used to find contaminants in organic matters and water and are easier genetically engineered with orthologous-mutated genes to explore specific proteins involved in proliferative and hormonal disturbances, chemotherapy multidrug resistance, and carcinogenicity. As multicellular embryos, larvae, and mature organisms, they can be tested in bigger-sized replication platforms with 24-, 96-, or 384-multiwell plates as cheaper and faster ways to select hit compounds from drug-like libraries to predict acute, subacute or chronic toxicity, pharmacokinetics, and efficacy parameters of pharmaceutical, cosmetic, and personal care products. Meanwhile, sublethal exposures are designed to identify changes in reproduction, body weight, DNA damages, oxidation, and immune defense responses in earthworms and zebrafishes, and swimming behaviors in A. salina and D. rerio. Behavioral parameters also give specificities on sublethal effects that would not be detected in zebrafishes by OECD protocols.

Cordia oncocalyx and oncocalyxones: From the phytochemistry to the anticancer action and therapeutic benefits against chronic diseases.

Cordia oncocalyx Allemão is an endemic economically underexploited plant from Brazilian semi-arid region. Herein, we carried out a well-defined bibliographic review about the pharmacological activities of oncocalyxones from C. oncocalyx and mechanisms responsible for the biomedical properties. MeSH terms were used in the scientific databases for a narrative exploration. Technological development and bioproducts were also examined. Cordia oncocalyx is a deciduous tree of sexual reproduction rich in terpenoid quinones. Among them, oncocalyxone A, a 1,4-benzoquinone, the main compound from heartwood ethanol extracts, revealed anti-inflammatory and anti-edematogenic actions induced by carrageenan and dextran and antinociceptive potential in mice provoked by acetic acid and formalin. Oncocalyxone A inhibits platelet aggregation via activation of the soluble guanylate cyclase enzyme and blocks glycation processes. In addition to the antimicrobial effects against protozoa, fungi and bacteria and relaxation of smooth muscles, oncocalyxone A reduces mean blood pressure and glycemia in diabetic rats, decreases glomerular filtration parameters and tubular transport of electrolytes, and presents in vitro antimitotic and cytotoxic action upon different types of cancers, including resistant lung carcinoma lines. It has low oral acute toxicity (LD50 > 2000 mg/kg) and activates cellular apoptosis through the production of free radicals and interactions with DNA. However, no patents were found, which also emphasizes that Brazil, as the cradle of the main articles on C. oncocalyx, is wasting time and money. Moreover, slight systemic deleterious effects in mammals stimulate the use of oncocalyxone A and related compounds as lead constituents of safer drugs against chronic diseases.