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沙特民间草药刺山柑对大鼠的急性和亚急性毒性作用评估

Assessment of acute and subacute toxic effects of the Saudi folk herb Retama raetam in rats.

作者信息

Algandaby Mardi M

机构信息

Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

J Chin Med Assoc. 2015 Dec;78(12):691-701. doi: 10.1016/j.jcma.2015.06.011. Epub 2015 Aug 1.

DOI:10.1016/j.jcma.2015.06.011
PMID:26239149
Abstract

BACKGROUND

Retama raetam (RR) fruit is used in traditional Saudi folk medicine as a hypoglycemic herb. However, the potential toxicity of RR has not been fully investigated. The current study aimed to explore the potential acute and subacute toxicities of the methanolic extract of RR fruit in male and female rats.

METHODS

The extent of acute toxicity of RR was tested 14 days after a single oral dose was administered (250 mg/kg, 500 mg/kg, or 750 mg/kg). Additionally, subacute toxicity was tested 28 days after an oral dose of 250 mg/kg/d, 500 mg/kg/d, or 750 mg/kg/d was administered for 4 weeks.

RESULTS

Subsequent to variable dosage testing, oral LD50 of RR was found to be 1995 mg/kg in rats. Oral doses of 500 mg/kg and 750 mg/kg significantly decreased body weight gain. Subacute administration (750 mg/kg) was associated with significant manifestations of toxicity. Additionally, subacute administration of the extract at doses of 500 mg/kg or 750 mg/kg significantly elevated alanine transaminase and aspartate transaminase activities. Hepatotoxicity of RR was confirmed with histopathological findings. Subacute administration of RR (500 mg/kg) showed histopathological changes in the liver as indicated by degenerated hepatocytes and early fibrosis, while a dosage of 750 mg/kg showed congested central vein and vascular degeneration. Moreover, subacute administration of the extract at doses of 250 mg/kg, 500 mg/kg, or 750 mg/kg showed histopathological alterations in rat kidney that ranged from mild interstitial congestion to tubular degeneration. The extract showed positive result in the Ames test.

CONCLUSION

Repeated administration of methanolic extract of RR (250 mg/kg) has a low nephrotoxic subacute toxicity potential, while it might have hepatotoxic, nephrotoxic, and mutagenic effects at higher doses.

摘要

背景

刺蒺藜果实(RR)在沙特传统民间医学中被用作降血糖草药。然而,RR的潜在毒性尚未得到充分研究。本研究旨在探讨RR果实甲醇提取物对雄性和雌性大鼠的潜在急性和亚急性毒性。

方法

单次口服给药(250mg/kg、500mg/kg或750mg/kg)14天后测试RR的急性毒性程度。此外,口服剂量为250mg/kg/d、500mg/kg/d或750mg/kg/d,给药4周,28天后测试亚急性毒性。

结果

经过不同剂量测试后,发现RR在大鼠中的口服半数致死量(LD50)为1995mg/kg。口服剂量500mg/kg和750mg/kg显著降低体重增加。亚急性给药(750mg/kg)伴有明显的毒性表现。此外,500mg/kg或750mg/kg剂量的提取物亚急性给药显著提高了丙氨酸转氨酶和天冬氨酸转氨酶活性。RR的肝毒性通过组织病理学检查得到证实。RR亚急性给药(500mg/kg)显示肝脏出现组织病理学变化,表现为肝细胞变性和早期纤维化,而750mg/kg剂量显示中央静脉充血和血管变性。此外,250mg/kg、500mg/kg或750mg/kg剂量的提取物亚急性给药显示大鼠肾脏出现组织病理学改变,范围从轻度间质充血到肾小管变性。该提取物在艾姆斯试验中呈阳性结果。

结论

RR甲醇提取物重复给药(250mg/kg)具有较低的亚急性肾毒性潜力,而在较高剂量时可能具有肝毒性、肾毒性和致突变作用。

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