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Purpose:  Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities.  Methods:  In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses.  Results:  The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morphological and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA) level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a significant reduction of serum urea level (p&lt;0.05), kidney's xanthine dehydrogenase (XDH) activity (p&lt;0.001) and elevation of aldehyde oxidase (AO) activity (p&lt;0.05) in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epithelium stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies.  Conclusion:  This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administration of JRSME may improve kidney structure and function and help in treatment of some chronic diseases.

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