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.

摘要
尽管麻黄碱已在诸多国家被禁止使用，但膳食补充剂与减重产品中同时添加对羟福林（p-synephrine）、麻黄碱（ephedrine）、水杨苷（salicin）与咖啡因（caffeine）的情况在全球范围内仍十分普遍。本研究旨在评估按质量比10:4:6:80（对羟福林:麻黄碱:水杨苷:咖啡因）混合的四组分混合物，对雌雄Wistar大鼠经口暴露28天的毒性特征。
实验每日记录大鼠体重、毒性体征、发病率与死亡率。暴露28天后，对所有大鼠实施安乐死并采集血液样本，用于血液学、生物化学与氧化应激指标检测。
结果显示，本实验未观察到明显毒性临床体征、显著体重下降或死亡案例，血液学参数亦无显著性改变。生物化学与氧化应激生物标志物检测结果表明：100mg/kg与150mg/kg剂量的雄性大鼠组出现脂质过氧化、肝肾功能损伤（p < 0.05; 方差分析（ANOVA）/邦费罗尼（Bonferroni）校正）；所有雄性剂量组大鼠的谷胱甘肽（GSH）水平均出现显著性下降（p < 0.05; 方差分析（ANOVA）/邦费罗尼（Bonferroni）校正）。各雌性剂量组未观察到氧化应激相关指标异常或生物化学参数改变。雌雄大鼠呈现出截然不同的毒性特征，提示该混合物的毒性效应受激素水平调控。本研究结果证实，受试混合组分可改变机体氧化状态，并诱发肝肾功能损伤。