Available online at www.sciencedirect.com Journal of Ethnopharmacology 115 (2008) 131–139 Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats Simoni Obici a,∗ , Fernanda Jacques Otobone a , Vˆ ania Ramos da Silva Sela a , Kelly Ishida b , Jos´ e Carlos da Silva c , Celso Vataru Nakamura b , Di ´ ogenes Apar´ ıcio Garcia Cortez a , Elisabeth Aparecida Audi a a Departamento de Farm´ acia e Farmacologia, Universidade Estadual de Maring´ a, Maring ´ a, Paran´ a, Brazil b Departamento de An ´ alises Cl´ ınicas, Universidade Estadual de Maring´ a, Maring ´ a, Paran´ a, Brazil c Departamento de Medicina, Universidade Estadual de Maring´ a, Maring ´ a, Paran´ a, Brazil Received 1 February 2007; received in revised form 12 September 2007; accepted 18 September 2007 Available online 25 September 2007 Abstract Kielmeyera coriacea Mart. (Clusiaceae), known as “Pau Santo” or “Saco de Boi” in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD 50 values of 1503.0 and 538.8mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Animal toxicity; Dichloromethane; Folk medicine; Kielmeyera coriacea; Phytotherapeutic 1. Introduction Kielmeyera coriacea Mart. (Clusiaceae) is known as “Pau Santo” or “Saco de Boi” in the central Brazilian plateau region. The aqueous extract is used in popular folk medicine for treatment of several tropical diseases, including schis- Abbreviations: DcM, dichloromethane; HE, hydroethanolic; HPLC, high- performance liquid chromatography; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; RBC, erythrocyte count; MCV, mean corpuscular volume; MCH, mean cor- puscular haemoglobin; MCHC, mean corpuscular haemoglobin concentration; WBC, leucocyte count; OFT, open-field test. ∗ Corresponding author at: Laborat´ orio de Neuropsicofarmacologia, Depar- tamento de Farm´ acia e Farmacologia, Universidade Estadual de Maring´ a, Av. Colombo 5790, CEP 87020-900 Maring´ a, Paran´ a, Brazil. Tel.: +55 44 3261 4844; fax: +55 44 3261 4999. E-mail addresses: simoniobici@yahoo.com.br (S. Obici), eaaudi@uem.br (E.A. Audi). tosomiasis, leishmaniasis, malaria, and fungal and bacterial infections (Alves et al., 2000). Previous studies performed in our laboratory showed that hydroethanolic (HE, 60 mg/kg) and dichloromethane (DcM, 5 mg/kg) extracts of Kielmey- era coriacea stems reduced immobility time when chronically administered (45 days) by gavage in rats submitted to the forced swimming test (FST), suggesting an antidepressant-like effect (Martins et al., 2004, 2006). The HE extract showed interaction with serotoninergic neurotransmission. In synaptosomal tests in vitro, the HE extract inhibited uptake of [ 3 H] serotonin (5- HT), [ 3 H] noradrenaline (NA), and [ 3 H] dopamine (DA) in a concentration-dependent manner (Goulart et al., 2007). The similarity of the biochemical mechanism to that of the classi- cal antidepressant drugs, despite the different selectivity seen among these compounds, indicates that this medicinal plant may be an alternative phytotherapeutic for the treatment of slight to moderate depression. An example is the known activ- ity of Hypericum perforatum, a member of the same family as 0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2007.09.013