槟榔多糖多酚对大鼠的亚慢性毒性研究

Sub-chronic toxicity of polyphenol and polysaccharid extracts from Areca catechu in Wistar rats

目的:研究槟榔多糖多酚对大鼠的亚慢性毒性作用,为槟榔的开发利用提供毒理学依据。方法:SPF级Wistar大鼠100只,雌雄各半,随机分为4组:0.28和0.83 g/kg槟榔多糖多酚组,每组20只,染毒90 d后处死;2.50 g/kg槟榔多糖多酚组和对照组,每组30只,其中20只在染毒90 d后处死,10只在染毒90 d后停止给予受试物,进入恢复期继续正常饲养28 d。染毒期间按10 mL/kg连续灌胃90 d,每天1次,对照组给予等体积蒸馏水。每周称量大鼠体质量和进食量,计算食物利用率,分别于染毒期和恢复期结束后检测血常规、血生化、尿液指标,大鼠麻醉后解剖进行大体观察、计算主要脏器的脏器系数并进行组织病理学检查。结果:2.50 g/kg槟榔多糖多酚组大鼠染毒期体质量总增量低于对照组,除雄性大鼠第1周食物利用率低于对照组(P<0.05)外,其余各周大鼠的食物利用率与对照组比较差异无统计学意义(P>0.05)。2.50 g/kg槟榔多糖多酚组雌雄大鼠各有5只于灌胃第3周出现精神欠佳、被毛不顺、胃肠胀气、活动减少等症状,于90 d染毒期间各死亡2只,于濒死前解剖肉眼可见胃肠胀气、胃肠壁变薄呈透明状,但主要脏器组织病理学检查未见明显异常。其他剂量组大鼠在90 d染毒期及恢复期与对照组比较未见明显异常,血常规、血生化、尿液个别指标与对照组比较虽有统计学差异,但均在本实验室正常检测值范围内,无生物学意义。主要脏器系数和组织病理学检查未见明显异常。考虑大鼠的死亡可能为大剂量槟榔多糖多酚引起胃肠胀气严重导致进食及消化受阻所致。在本试验条件下,槟榔多糖多酚灌胃Wistar大鼠90 d,未观察到有害作用剂量(NOAEL)为0.83 g/kg。结论:2.50 g/kg槟榔多糖多酚灌胃90 d可引起Wistar大鼠精神萎靡、胃肠胀气、进食及消化受阻,此症状虽可逆,但剂量过高可致死亡,因此槟榔多糖多酚的开发利用需控制在安全剂量范围内。

OBJECTIVE:To investigate sub-chronic toxicity of polyphenol and polysaccharide extracts from Areca catechu in Wistar rats.METHODS:A total of 100 Wistar rats were randomly divided into control group,and Areca polysaccharide polyphenols-treated groups:0.28,0.83 and 2.5 g/kg.From the 0.28 and 0.83g/kg groups,20 in each group,were killed after 90 days of exposure.From the 2.50 g/kg and control groups(30 in each group),20 were killed after 90 days of exposure,and treatments were stopped for the remaining10 which received normal feeding for the subsequent 28 days.Each treated rat received 10 mL/kg volume of continuous intragastric administration for 90 days,once a day,and the control rats received equal volume of distilled water.Changes of body weight,food availability,hematology,biochemical parameters,urinalysis,main organ coefficient and histopathological examination were detected.RESULTS:Total weight gain of the2.50 g/kg group was lower than that of the control group during the treatment period.There were no significant differences in the food utilization rates between groups except that the male rats in the first week of 2.50 g/kg group was lower than that in the control group.Five male and five female rats in the 2.50 g/kg group showed symptoms of poor spirit,rough coat and sluggish reaction after 3 weeks of treatment.Two male and two female rats died during the treatment period.Flatulence and thinning of gastrointestinal wall were observed in nakedrats,but no obvious abnormalities were found in the histopathological examination of major organs.There wereno obvious abnormalities in other dose groups compared with the control group during the exposure and therecovery periods.Although there were statistical differences in hematology,blood biochemistry and individualurine indexes between the control and the other dose groups,they were all within the range of normal testvalues in our laboratory,and had no biological significance.The organ coefficient and histopathologicalexamination of the main organs showed no obvious abnormalities.It was considered that the death of rats mighthave been caused by gastrointestinal flatulence due to intestinal fermentation of a large amount ofpolysaccharide.Under the conditions of this study,90-day oral treatment with 0.83 g/kg areca polysaccharidepolyphenols was considered to be at the no observed adverse effect level(NOAEL).CONCLUSION:Oraladministration of 2.50 g/kg areca polysaccharides polyphenols for 90 days caused lethargy and flatulence inWistar rats.Although this symptom was reversible,excessive dosage caused mortality.Therefore,developmentand utilization of areca polysaccharides polyphenols should be controlled within the safe dose range.