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光叶墙草叶水提取物对啮齿动物的急性和亚慢性毒性

Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents.

作者信息

Rhiouani Hamid, El-Hilaly Jaouad, Israili Zafar H, Lyoussi Badiâa

机构信息

Laboratory of Physiology-Pharmacology and Environmental Health, Department of Biology, Faculty of Sciences, Dhar El Mehraz, Fez, Morocco.

出版信息

J Ethnopharmacol. 2008 Aug 13;118(3):378-86. doi: 10.1016/j.jep.2008.05.009. Epub 2008 May 15.

Abstract

AIM OF THE STUDY

The present investigation was carried out to evaluate the safety of an aqueous extract of Herniaria glabra (caryophyllaceae) (HG) plant by determining its potential toxicity after acute and sub-chronic administration in rodents.

MATERIALS AND METHODS

For the acute study, a lyophilized aqueous extract of HG plant was administered to adult IOPS OFA mice in single doses of 5-14.5 g/kg given by gavage. General behavior adverse effects and mortality were determined for up to 14 days. In the sub-chronic dose study, the HG-extract was administered orally at doses of 1, 2 and 4 g/kg daily for 90 days to Wistar rats. Selected biochemical and hematological parameters were determined after 30 and 60 days, and then at the end of 90 days of daily administration.

RESULTS

In the acute study in mice, the crude aqueous extract of HG plant caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the HG extract was 5 g/kg and the lowest-observed adverse effect levels (LOAEL) was 5.5 g/kg. Mortality increased with increasing doses: the calculated LD50 was 8.50 +/- 0.42 g/kg in mice. In the sub-chronic study in rats, daily oral administration of the crude HG extract for up to 90 days resulted in a significant attenuation of the normal increase in the body weight. At the highest dose, the HG-extract caused a significant increase in erythrocytes, leukocytes (WBC), platelets, and eosinophils, but it had no effect on the differential WBC counts (lymphocytes, monocytes, neutrophils and basophils). Only at the highest dose, the HG-extract caused a significant increase in serum levels of the liver enzymes, alanine aminotransferase and aspartate aminotransferase, as well as serum creatinine, indicating toxic effect of the high dose of the extract on the liver and kidney. The organ toxicity was confirmed by histopathological examination, which showed centrolobular sinusoidal congestion, disruption of the central vein and hepatocellular necrosis in the liver, and interstitial and intraglomerular congestion, tubular atrophy, and inflammation in the kidney. This study also revealed the hypoglycemic activity of the HG-extract in normoglycemic rats. The suppression of the normal weight gain and the hypoglycemic action of HG-extract should be investigated further for possible therapeutic implications.

CONCLUSIONS

Because of the relatively high NOAEL values in the acute study in mice, and lack of mortality or clinically significant changes in the biological (except for hypoglycemia) and hematological parameters in rats after 90 days of daily dosing, it may be concluded that the HG extract does not appear to have significant toxicity (except at high doses). In view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Herniaria glabra.

摘要

研究目的

本研究旨在通过测定地锦草(石竹科)水提取物(HG)在啮齿动物急性和亚慢性给药后的潜在毒性,评估其安全性。

材料与方法

在急性研究中,将HG植物的冻干水提取物以5 - 14.5 g/kg的单剂量通过灌胃给予成年IOPS OFA小鼠。观察长达14天的一般行为不良反应和死亡率。在亚慢性剂量研究中,将HG提取物以1、2和4 g/kg的剂量每日口服给予Wistar大鼠,持续90天。在每日给药30天和60天后,以及90天结束时,测定选定的生化和血液学参数。

结果

在小鼠急性研究中,HG植物的粗水提取物引起剂量依赖性的一般行为不良反应和死亡率。HG提取物的未观察到不良反应水平(NOAEL)为5 g/kg,最低观察到不良反应水平(LOAEL)为5.5 g/kg。死亡率随剂量增加而增加:小鼠的计算半数致死量(LD50)为8.50±0.42 g/kg。在大鼠亚慢性研究中,每日口服粗HG提取物长达90天导致体重正常增加显著减弱。在最高剂量下,HG提取物导致红细胞、白细胞(WBC)、血小板和嗜酸性粒细胞显著增加,但对白细胞分类计数(淋巴细胞、单核细胞、中性粒细胞和嗜碱性粒细胞)无影响。仅在最高剂量下,HG提取物导致血清肝酶丙氨酸氨基转移酶和天冬氨酸氨基转移酶以及血清肌酐水平显著升高,表明高剂量提取物对肝脏和肾脏有毒性作用。组织病理学检查证实了器官毒性,显示肝脏中央小叶窦状充血、中央静脉破坏和肝细胞坏死,以及肾脏间质和肾小球内充血、肾小管萎缩和炎症。本研究还揭示了HG提取物在血糖正常的大鼠中的降血糖活性。HG提取物对正常体重增加的抑制作用和降血糖作用应进一步研究其可能的治疗意义。

结论

由于小鼠急性研究中NOAEL值相对较高,且大鼠每日给药90天后在生物学(除低血糖外)和血液学参数方面无死亡或临床显著变化,因此可以得出结论,HG提取物似乎没有显著毒性(高剂量除外)。鉴于摩洛哥传统医学中经验性使用的剂量,地锦草治疗应用的安全范围很宽。

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