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评价关木通水提物急性和亚急性暴露的潜在毒性。(马兜铃科)

Evaluation of the toxicity potential of acute and sub-acute exposure to the aqueous root extract of Aristolochia ringens Vahl. (Aristolochiaceae).

机构信息

Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, University of Lagos, P.M.B. 12003, Idi-Araba, Surulere, Lagos, Nigeria.

Department of Pharmacognosy, Faculty of Pharmacy, College of Medicine, University of Lagos, P.M.B. 12003, Idi-Araba, Surulere, Lagos, Nigeria.

出版信息

J Ethnopharmacol. 2019 Nov 15;244:112150. doi: 10.1016/j.jep.2019.112150. Epub 2019 Aug 8.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Aristolochia ringens Vahl. (Aristolochiaceae) is used traditionally in Nigeria for managing a number of ailments including gastrointestinal disturbances, rheumatoid arthritis, pile, insomnia, oedema, and snake bite venom. Some studies in our laboratory have demonstrated a scientific justification for some of such uses. This study aims at investigating the toxicological actions of the aqueous root extract of Aristolochia ringens (AR).

MATERIALS AND METHODS

Brine shrimp lethality assay was carried out using 10, 100 and 1000 μg/ml of the extract. Oral and intraperitoneal acute toxicity tests were carried out using mice. The effect of sub-acute (30 days) repeated oral exposure to the extract at 10, 50 and 250 mg/kg in rats was also evaluated via weekly assessments of body weights and general observations as well as end of exposure haematological, biochemical and histological examinations of blood and tissue samples of treated rats. Phytochemical analyses to determine the presence of aristolochic acid I in the extract was also carried out using high performance liquid chromatography (HPLC).

RESULTS

The aqueous root extract of A. ringens showed potential for biological activity and cytotoxicity with an LC of 175 μg/ml in brine shrimps. AR was found to be relatively safe on acute oral exposure with LD estimated to be greater than 10 g/kg, while its LD on intraperitoneal administration was 407.38 mg/kg. Upon 30 days sub-chronic exposure, AR induced significant weight loss in female rats, enlargement of male rats' stomach, oxidative stress in male and female rats' kidney and liver tissues and disruption of leukocytes level in female rats. It also showed evidence of kidney and liver injuries inducible by oxidative damage and the potential to cause male sterility. HPLC revealed the presence of 0.003 mg/1 g of aristolochic acid in AR.

CONCLUSION

These results show that AR contains detectible aristolochic acid I and has potential to induce toxic responses. Caution must therefore be exercised in its medicinal application especially when required for a prolonged use.

摘要

民族药理学相关性

Aristolochia ringens Vahl.(马兜铃科)在尼日利亚传统上用于治疗多种疾病,包括胃肠道紊乱、类风湿性关节炎、痔疮、失眠、水肿和蛇咬伤毒液。我们实验室的一些研究已经证明了其中一些用途的科学依据。本研究旨在研究 Aristolochia ringens(AR)水根提取物的毒理学作用。

材料和方法

使用 10、100 和 1000μg/ml 的提取物进行盐水虾致死性测定。使用小鼠进行口服和腹腔内急性毒性试验。还通过每周评估体重和一般观察以及暴露结束时对治疗大鼠的血液和组织样本进行血液学、生化学和组织学检查,评估亚急性(30 天)重复口服暴露于提取物(10、50 和 250mg/kg)的影响。还使用高效液相色谱法(HPLC)进行了植物化学分析,以确定提取物中是否存在马兜铃酸 I。

结果

A. ringens 的水根提取物在盐水虾中具有潜在的生物活性和细胞毒性,LC 为 175μg/ml。AR 在口服急性暴露时相对安全,LD 估计大于 10g/kg,而腹腔内给药的 LD 为 407.38mg/kg。在 30 天的亚慢性暴露期间,AR 导致雌性大鼠体重减轻、雄性大鼠胃肿大、雄性和雌性大鼠肾脏和肝脏组织的氧化应激以及雌性大鼠白细胞水平紊乱。它还显示出由氧化损伤引起的肾脏和肝脏损伤以及导致雄性不育的证据。HPLC 显示 AR 中含有 0.003mg/1g 的马兜铃酸 I。

结论

这些结果表明 AR 含有可检测的马兜铃酸 I,并且具有引起毒性反应的潜力。因此,在其药用应用中必须谨慎,特别是在需要长期使用的情况下。

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