Toxicological studies of gambogic acid and its potential targets in experimental animals.
Acute and chronic toxicity of gambogic acid, a promising novel anticancer agent, was determined using albino mice and Beagle dogs as model animals. Histopathological examination and viscera parameter investigation were also carried out after autopsy. The LD50 of gambogic acid was found to be 45 approximately 96 mg/kg and the 95% confidence limit was determined to be 43.18 approximately 48.45 mg/kg. The results from the chronic toxicity studies demonstrated that the toxicity targets in the experimental animals were liver and kidney. The innocuous dose was established to be 4 mg/kg after administration to dogs for a total of 13 weeks at a frequency of one injection every other day. This dose (4 mg/kg) was approximately 9.6 (body weight) or 5.1 (body surface area) times the dosage (25 mg/60 kg, every other day) recommended for human trials. Our results provide the theoretical foundation for clinical applications of this promising natural anticancer agent and will likely bring about considerable economic and social benefits.
Guo
Qinglong
Q
Department of Physiology, China Pharmaceutical University, 24 Tongjian Xiang, Nanjing 210009, China.
Qi
Qi
Q
You
Qidong
Q
Gu
Hongyan
H
Zhao
Li
L
Wu
Zhaoqiu
Z
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D023421:Models, Animal; D015394:Molecular Structure; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D013997:Time Factors; D023382:Toxicity Tests, Acute / Q000379:methods*; D036401:Toxicity Tests, Chronic / Q000379:methods*; D015431:Weight Loss / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*
D015415:Biomarkers; D044004:Xanthones; C052659:gambogic acid