Gender differences in biochemical markers and oxidative stress of rats after 28 days oral exposure to a mixture used for weight loss containing p-synephrine, ephedrine, salicin, and caffeine

ABSTRACT The association of p-synephrine, ephedrine, salicin, and caffeine in dietary supplements and weight loss products is very common worldwide, even though ephedrine has been prohibited in many countries. The aim of this study was to evaluate a 28-day oral exposure toxicity profile of p-synephrine, ephedrine, salicin, and caffeine mixture (10:4:6:80 w/w respectively) in male and female Wistar rats. Body weight and signs of toxicity, morbidity, and mortality were observed daily. After 28 days, animals were euthanized and blood collected for hematological, biochemical, and oxidative stress evaluation. No clinical signs of toxicity, significant weight loss or deaths occurred, nor were there any significant alterations in hematological parameters. Biochemical and oxidative stress biomarkers showed lipid peroxidation, and hepatic and renal damage (p < 0.05; ANOVA/Bonferroni) in male rats (100 and 150 mg/kg) and a reduction (p < 0.05; ANOVA/Bonferroni) in glutathione (GSH) levels in all male groups. Female groups displayed no indications of oxidative stress or biochemical alterations. The different toxicity profile displayed by male and female rats suggests a hormonal influence on mixture effects. Results demonstrated that the tested mixture can alter oxidative status and promote renal and hepatic damages.

RESUMO A associação de p-sinefrina, efedrina, salicina, e cafeína em suplementos alimentares e produtos para perda de peso é muito utilizada em todo o mundo, embora a efedrina tenha sido proibida em muitos países. O objetivo deste estudo foi avaliar o perfil de toxicidade à exposição oral de 28 dias à associação de p-sinefrina, efedrina, salicina e cafeína (na proporção de 10:4:6:80 m/m respectivamente) em ratos Wistar machos e fêmeas. Diariamente, os animais foram observados quanto ao peso corporal, sinais de toxicidade, morbidade e mortalidade. Após 28 dias, os animais foram sacrificados e o sangue coletado para avaliações hematológicas, bioquímicas e de estresse oxidativo. Não se observaram sinais clínicos de toxicidade, tampouco perda significativa de peso, mortes, ou quaisquer alterações significativas nos parâmetros hematológicos. Biomarcadores do estresse oxidativo e bioquímicos mostraram peroxidação lipídica, danos renais e hepáticos (p < 0,05; ANOVA/Bonferroni) em ratos machos (100 e 150 mg/kg) e a redução (p < 0,05; ANOVA/Bonferroni) nos níveis de glutationa reduzida (GSH) em todos os grupos de machos tratados. Nas fêmeas, não houve indícios de estresse oxidativo, nem alterações bioquímicas. O diferente perfil de toxicidade entre os gêneros sugere influência hormonal nos efeitos de mistura administrada. A associação testada pode alterar o estado oxidativo e promover danos renais e hepáticos.

Biological assessment (antiviral and antioxidant) and acute toxicity of essential oils from Drimys angustifolia and D. brasiliensis

The genus Drimys presents the widest geographical distribution of the Winteraceae family, which comprises seven genera and about 120 species. In Brazil, the genus is found from Bahia to Rio Grande do Sul and occur in two species, Drimys angustifolia Miers, and D. brasiliensis Miers, Winteraceae, popularly known as "casca-de-anta", characterized by the presence of flavonoids and essential oils. It is used in folk medicine as an antiscorbutic, stimulant, antispasmodic, anti-diarrheal, antipyretic, antibacterial, and against asthma and bronchitis, besides having insecticidal properties. In addition to the known biological activities, it is very important to explore new applications in the treatment of physiological disorders or diseases caused by parasites. Based on this information, in this study we propose to evaluate volatile oils of the species D. brasiliensis and D. angustifolia, as an antioxidant, using the model of the DPPH radical as an antiviral against human herpes virus type 1 (HSV-1) and acute toxicity in vivo. The two species were not able to reduce the DPPH radical and showed interesting antiviral activity, significantly reducing the virus titers in vitro assays. Regarding the in vivo toxicity in female Wistar rats, treatment with the two species showed interesting signs in animals such as salivation, ptosis, tremor, decreased motor activity. In addition the oils of D. brasiliensis to other signs, some animals showed increased urination and diarrhea.