Studies on the toxicity of gambogic acid in rats.
OBJECTIVE
To study the chronic toxicity of gambogic acid (GA), the major active ingredient of gamboges, a brownish to orange resin extracted from the Garcinia hanburyi (family Guttiferae) in Southeast Asia, using Sprague-Dawley rat as an animal model and provide further theoretical support for clinical applications of this promising natural anticancer agent.


METHODS
GA was administered orally at dosages of 120, 60 and 30 mg/kg once every other day for a total of 13 weeks. Then we carried out the chronic toxicity studies including general body parameters, hematological, serum biochemistry, histopathological, and viscera examination.


RESULTS
The results from the studies demonstrated that rats treated with high dose (120 mg/kg) of GA for a long time can lead to the damage on the kidney and liver. An innocuous dose was established to be 60 mg/kg after administration to rats for a total of 13 weeks at a frequency of one administration every other day. This dose was approximately 18.0 (body weight) or 9.6 (body surface area) times higher then that of the dose (200mg/60 kg, every other day) used for human trials.


CONCLUSIONS
The studies demonstrated that the toxicity targets in the rats were the kidney and liver. These results provide further theoretical support for clinical applications of this promising natural anticancer agent.
Qi
Qi
Q
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu 210009, People's Republic of China.
You
Qidong
Q
Gu
Hongyan
H
Zhao
Li
L
Liu
Wei
W
Lu
Na
N
Guo
Qinglong
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D005260:Female; D029760:Garcinia / Q000737:chemistry; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044004:Xanthones / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D044004:Xanthones; C052659:gambogic acid