ACUTE AND SUB-CHRONIC (28 DAYS) REPEATED ORAL TOXICITY TEST OF ETHANOL EXTRACT OF LERAK (SAPINDUS RARAK. DC) FRUITS IN WISTAR RATS
Keywords:Acute toxicity, Sub-chronic 28 days repeated oral toxicity, Ethanol extract lerak fruits (EELF)
Objectives: Natural product which is used as medicines should in compliance with the guidelines that the drug does not cause acute or chronic toxicity and proved efficacious as a medicinal. The present study was carried out to evaluate the safety of ethanol extract of lerak (sapindus rarak. DC) fruits.
Methods: Lerak fruits were extracted by continuous extraction using the Soxhlet apparatus and ethanol 96 %. Extraction results was continued to acute toxicity by using a fixed dose method and sub-chronic toxicity was performed according to the OECD guideline. In an acute toxicity study, a single dose of 2000 and 5000 mg/kg bw of lerak fruits extract was administered p. o (orally) to healthy female Wistar rats following a sighting study. The animals were observed for mortality and clinical signs for 24 hour and then daily for 14 days. In the sub-chronic toxicity study, the extract was administered orally at doses of 50, 100 and 500 mg/kg bw /day. The animals were given by ethanol extract of lerak fruits once daily for 28 days, the administrations were stopped on the 28th day, while for the satellite group still observed until 14 days during the post observation period for assessment of reversibility, persistence or delayed occurrence of toxicity. At the end of the observation, all animals were autopsied and observed in parameters such as blood biochemical parameters, hematology, urine profiles, physical pathology and histological examination.
Results: In the acute toxicity test, oral administration of 2000 and 5000 mg/kg bw produced neither mortality nor changes in behavior or any other physiological activities and indicated that LD50 of the ethanol extract of the lerak fruits (EELF) was greater than 5000 mg/kg bw in Wistar rats. In sub-chronic 28-days repeated dose oral toxicity study, administration of ethanol extract lerak fruits with dose of 50 mg/kg bw, 100 mg/kg bw, 500 mg/kg bw in male and female rats generally showed no significantly differences in parameters abnormalities of organ function, behavior and motor activity, urine parameters, blood biochemical parameters, condition of the gastric mucosa, histology and did not produce mortality in treated groups compared to control group. Ethanol extract of lerak fruits with the dose of 500 mg/kg bb showed increasing in SGOT, decreased in cholesterol and body weight in male and female rats. Obvious histological changes were observed in the heart and liver organ of lerak fruits dose 500 mg/kg bw extract treated animals compared to control.
Conclusions: Based on the finding of this study, the no-observed-adverse-effect-level (NOAEL) of EELF in wistar rats, following oral administration for 28 days was found to be more than 100 mg/kg bw.
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