title: Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent.
abstract: BACKGROUND
  Mitragyna speciosa Korth (ketum) is widely used in Malaysia as a medicinal agent for treating diarrhea, worm infestations and also acts as an analgesic and antipyretic.
  
  
  OBJECTIVE
  The aim of the study is to determine the acute toxicity of Mitragyna speciosa Korth standardized methanol extract in vivo in 4-weeks-old Sprague-Dawley rats.
  
  
  METHODS
  Rats were orally administrated single dose of 100, 500 and 1000 mg/kg Mitragyna speciosa Korth standardized methanol extract and the control group received 430 mg/kg of morphine orally. There were 10 rats in each group. All animals were sacrificed after 14 days of treatment. Eight parameters were tested: cage side observation, body weight measurement, food and water consumption, blood pressure, absolute and relative organ weight, hematology, biochemical analysis and histopathology, to look for evidence of toxicity.
  
  
  RESULTS
  No mortality was noted after 14 days of treatment. In general, behavior, food and water consumption, hematological studies and organ weights showed no significant changes. The standardized methanol extraction of Mitragyna speciosa Korth increased rat blood pressure (systolic: 147.4+/-1.01, 131.64+/-4.94 and 137.8+/-4.46) after an hour of 100, 500 and 1000 mg/kg doses, respectively. Biochemical studies showed significant elevation of ALT, AST, albumin, triglycerides, cholesterol and albumin (p>0.05), at all levels of doses. But, nephrotoxicity evidenced by elevated creatinine was seen only at a dose of 1000 mg/kg. Histological examination showed congestion of sinusoids, hemorrhage hepatocytes, fatty change, centrilobular necrosis and increased number of Kuppfer cells in the liver of all Mitragyna speciosa Korth standardized methanol extract treated groups.
  
  
  CONCLUSIONS
  Oral administration of standardized methanolic extraction of Mitragyna speciosa Korth resulted in increasing rat blood pressure after an hour of drug administration. The highest dose of extract also induced acute severe hepatotoxicity and mild nephrotoxicity. However, Mitragyna speciosa Korth shows no effects on body weight, food and water consumption, absolute and relative organ weight and also hematology parameters.
authors.affiliation: Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. mohdharizal@yahoo.com
authors.forename: S N
authors.initials: SN
authors.lastname: Harizal
authors.forename: S M
authors.initials: SM
authors.lastname: Mansor
authors.forename: J
authors.initials: J
authors.lastname: Hasnan
authors.forename: J K J
authors.initials: JK
authors.lastname: Tharakan
authors.forename: J
authors.initials: J
authors.lastname: Abdullah
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D032065:Mitragyna / Q000633:toxicity*; D010936:Plant Extracts / Q000633:toxicity*; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D008055:Lipids; D010936:Plant Extracts; D012709:Serum Albumin; D014280:Triglycerides; D002784:Cholesterol; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase