Regular consumption of polyphenol-rich fruits and vegetables is associated with beneficial health outcomes. To increase polyphenol intakes, consumers are increasingly using herbal and botanical dietary supplements containing concentrated polyphenol extracts. However, the safety of this consumption modality has not been vetted. To address this, ovariectomized Sprague-Dawley (OVX-SD) rats were orally gavaged with purified blueberry polyphenols at 0-1000 mg total polyphenols/kg bw/d for 90d. No differences in behavior, body weight, or food consumption were observed. No tumors or macroscopic changes were observed, and histopathological analyses showed no differences among groups. Although several statistically significant differences between treatment and control groups were observed in urine (color and pH) and blood (monocyte count, total cholesterol, and chloride ion concentration) analyses, these parameters were within normal ranges and not considered biologically significant. Intestinal permeability assessed via FITC-dextran showed increased intestinal permeability in the highest dose, though no morphological differences were found throughout the gastrointestinal tract. Given the lack of other systemic changes, this finding is likely of minimal physiological importance. These results indicate a NOAEL for blueberry polyphenols in OVX-SD rats is ≥ 1000 mg total polyphenols/kg bw/d, which translates to a 70 kg human consuming ~10 g polyphenols. Keywords: Blueberry, Polyphenol, Sub-chronic toxicity.

中文翻译：

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蓝莓多酚在卵巢切除的大白鼠身上的90天口服毒性研究。

经常食用富含多酚的水果和蔬菜与有益健康的结果有关。为了增加多酚的摄入，消费者越来越多地使用含有浓缩多酚提取物的草药和植物性膳食补充剂。但是，这种消费方式的安全性尚未得到审查。为了解决这个问题，将经卵巢切除的Sprague-Dawley（OVX-SD）大鼠以0-1000 mg总多酚/ kg bw / d口服纯化的蓝莓多酚90天。没有观察到行为，体重或食物消耗方面的差异。没有观察到肿瘤或宏观变化，并且组织病理学分析显示各组之间没有差异。尽管在治疗组和对照组之间在尿液（颜色和pH）和血液（单核细胞计数，总胆固醇，和氯离子浓度）分析，这些参数在正常范围内，不具有生物学意义。通过FITC-葡聚糖评估的肠通透性显示最高剂量时肠通透性增加，尽管在整个胃肠道中未发现形态学差异。由于缺乏其他全身性变化，这一发现可能具有最小的生理重要性。这些结果表明，在OVX-SD大鼠中蓝莓多酚的NOAEL为≥1000 mg总多酚/ kg bw / d，这意味着70公斤的人消耗了约10 g的多酚。关键字：蓝莓，多酚，亚慢性毒性。通过FITC-葡聚糖评估的肠通透性显示最高剂量时肠通透性增加，尽管在整个胃肠道中未发现形态学差异。由于缺乏其他全身性变化，这一发现可能具有最小的生理重要性。这些结果表明，在OVX-SD大鼠中蓝莓多酚的NOAEL为≥1000 mg总多酚/ kg bw / d，这意味着70公斤的人消耗了约10 g的多酚。关键字：蓝莓，多酚，亚慢性毒性。通过FITC-葡聚糖评估的肠通透性显示最高剂量时肠通透性增加，尽管在整个胃肠道中未发现形态学差异。由于缺乏其他全身性变化，这一发现可能具有最小的生理重要性。这些结果表明，在OVX-SD大鼠中蓝莓多酚的NOAEL为≥1000 mg总多酚/ kg bw / d，这意味着70公斤的人消耗了约10 g的多酚。关键字：蓝莓，多酚，亚慢性毒性。这些结果表明，在OVX-SD大鼠中蓝莓多酚的NOAEL为≥1000 mg总多酚/ kg bw / d，这意味着70公斤的人消耗了约10 g的多酚。关键字：蓝莓，多酚，亚慢性毒性。这些结果表明，在OVX-SD大鼠中蓝莓多酚的NOAEL为≥1000 mg总多酚/ kg bw / d，这意味着70公斤的人消耗了约10 g的多酚。关键字：蓝莓，多酚，亚慢性毒性。