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.Uniterms: p-Synephrine/toxicity profile. Ephedrine/toxicity profile. Salicin/toxicity profile. Caffeine/ toxicity profile. Dietary supplements/evaluation. Weight loss products/evaluation.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. Unitermos INTRODUCTIONOverweight and obesity are highly prevalent worldwide. Many consumers are seeking strategies for reducing weight to healt...

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“…Studies in mice also found that synephrine can cause toxin-induced liver injury in moderate amounts (≥100mg), eventually resulting in death with increased dosage amounts (≥350mg). The gender of the mice also played an important role in these studies, since liver toxicity and lethal amounts seemed to differ between males and females [18][19][20]. In this study, only one DS had synephrine in the form of Citrus aurantium extract (400mg), but these DS also had 350 mg of caffeine, increasing the possibility of unwanted cardiovascular side effects.…”

Acute and Subchronic Toxicological Study of the Cocktail Extract from Curcuma xanthorrhiza Roxb, Phyllanthus niruri L. and Morinda citrifolia L.

“…An investigation of the subchronic toxicity of plant-derived extracts on both male and female rats is needed due to distinct hormone responses. It is known that sex hormones can influence the response of the body to the tested natural products [ 74 ]. In addition, the inclusion of both male and female rats in this study may enhance the validity of the drug toxicity profile [ 75 ].…”

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“…Additionally, there are data to confirm that women’s responses to Citrus aurantium are of lower magnitude than those of men, with lower increases in energy expenditure and a diminished effect on reducing the respiratory quotient at rest [ 32 ]. Lastly, although there is no evidence in humans, a study comparing body weight evolution of male and female rats exposed to solutions containing p -synephrine, ephedrine, salicin, and caffeine (proportions of 10:4:6:80, respectively) for 28 days found that females were less susceptible to the effects of the p -synephrine-containing product on body weight fluctuations [ 33 ]. Collectively, all this information supports a potential sex-derived effect on the physiological outcomes derived from the intake of p -synephrine-containing products.…”