Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic
Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic
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DOI：
10.1021/jf020842c
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发表时间：
2003-05-21
影响因子：
6.1
通讯作者：
Espín, JC
中科院分区：
文献类型：
--
作者：
Cerdá, B;Cerón, JJ;Espín, JC
据报道，水溶性鞣花单宁安石榴苷对牛有毒。考虑到石榴汁中这种抗氧化多酚含量非常丰富（大于或等于2 g/L），本研究评价了Sprague-Dawley大鼠重复经口给予含6%安石榴苷的饲料37天后安石榴苷的可能毒性作用。通过HPLC-DAD-MS-MS鉴别了血浆、肝脏和肾脏中的红石榴苷和相关代谢产物。在肝脏和肾脏中检测到5种安石榴苷相关代谢产物，即两种鞣花酸衍生物、没食子酸、3，8-二羟基-6H-二苯并[B，d]吡喃-6-酮葡糖苷酸和3，8，10-三羟基-6H-二苯并[B，d]吡喃-6-酮。在前15天内，给药大鼠的饲料摄入量、食物利用指数和生长速率较低，无显著不良反应，这可能是由于富含安石榴苷的饲料的营养价值较低以及其适口性降低（摄食量较低）所致。在给药大鼠中，除尿素和甘油三酯（在整个实验期间保持低值）外，分析的任何血液参数（包括抗氧化酶谷胱甘肽过氧化物酶和超氧化物歧化酶）均无显著差异。尽管降低的原因尚不清楚，但可能是由于富含安石榴苷的饲料相对于标准大鼠饲料的营养价值较低。肝脏和肾脏的组织学分析证实无毒性。原则上，本文报告的结果以及考虑的较大安全范围表明，在研究的37天期间，安石榴苷对大鼠无毒性作用。然而，考虑到石榴酸衍生食品中安石榴苷含量较高，还应在人体中进行较低剂量和较长时间摄入的安全性评价。
The water-soluble ellagitanin punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (greater than or equal to 2 g/L), the present study evaluated the possible toxic effect of punicalagin in Sprague-Dawley rats upon repeated oral administration of a 6% punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found in treated rats in any blood parameter analyzed (including the antioxidant enzymes gluthatione peroxidase and superoxide dismutase) with the exception of urea and triglycerides, which remained at low values throughout the experiment. Although the reason for the decrease is unclear, it could be due to the lower nutritional value of the punicalagin-enriched diet with respect to the standard rat food. Histopathological analysis of liver and kidney corroborated the absence of toxicity. In principle, the results reported here, together with the large safety margin considered, indicate the lack of toxic effect of punicalagin in rats during the 37 day period investigated. However, taking into account the high punicalagin content of pomegranate-derived foodstuffs, safety evaluation should be also carried out in humans with a lower dose and during a longer period of intake.