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Journal of Ethnopharmacology
Volume 118, Issue 3, 13 August 2008, Pages 378-386
 
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doi:10.1016/j.jep.2008.05.009    
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Copyright © 2008 Elsevier Ireland Ltd All rights reserved.

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

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Hamid Rhiouania, Jaouad El-Hilalya, Zafar H. Israilib and Badiâa Lyoussia, Corresponding Author Contact Information, E-mail The Corresponding Author

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

bDepartment of Medicine, Emory University School of Medicine, Atlanta, GA, USA


Received 2 March 2007; 
revised 8 April 2008; 
accepted 1 May 2008. 
Available online 15 May 2008.

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.

Keywords: Herniaria glabra; Animal toxicity; Traditional medicine; Acute and sub-chronic dosing

Article Outline

1. Introduction
2. Materials and methods
2.1. Plant material
2.2. Preparation of the aqueous extract of Herniaria glabra whole plant
2.3. Experimental animals
2.4. Toxicological evaluation of the HG-extract
2.4.1. Acute toxicity studies in mice
2.4.2. Sub-chronic toxicity studies in rats
2.5. Measurement of biochemical and hematological parameters in blood
2.6. Histopathological examination of the liver and kidney tissues
2.7. Statistical analysis
3. Results
3.1. Acute toxicity
3.2. Sub-chronic toxicity studies of Herniaria glabra-extract in rats
3.2.1. Clinical observations and body weight of rats
3.2.2. Effect of sub-chronic treatment of rats with HG-extract on the biochemical and hematological parameters
3.2.3. Histopathological changes
4. Discussion and conclusion
References






Corresponding Author Contact InformationCorresponding author at: UFR: Physiology-Pharmacology and Environmental Health, Faculty of Sciences, USMBA, BP 1976, Atlas Fez 30000, Morocco. Tel.: +212 35 64 12 73.

Journal of Ethnopharmacology
Volume 118, Issue 3, 13 August 2008, Pages 378-386
 
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