Arzneimittelforschung 2008; 58(12): 673-680
DOI: 10.1055/s-0031-1296570
Immunomodulators · Immunostimulants · Immunosuppressants
Editio Cantor Verlag Aulendorf (Germany)

Male Reproductive Toxicity and Toxicokinetics of Triptolide in Rats

Bin Ni
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Zhenzhou Jiang
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Xin Huang
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Fengguo Xu
1  Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing (The People’s Republic of China)
,
Rui Zhang
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Zunjian Zhang
1  Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing (The People’s Republic of China)
,
Yuan Tian
1  Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing (The People’s Republic of China)
,
Tao Wang
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Tian Zhu
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Jing Liu
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
,
Luyong Zhang
1  National Drug Screening Center, China Pharmaceutical University, Nanjing (The People’s Republic of China)
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2011 (online)

Abstract

As the unique quality control standard of Tabellae Glucosidorum Tripterygii Totorum, triptolide (CAS 38748-32-2) has a narrow therapeutic window. A significant side-effect of triptolide is its male reproductive toxicity the mechanism of which is still unknown. Therefore, in the present study the male reproductive toxicity and toxicokinetics of triptolide were investigated. Male Sprague-Dawley (SD) rats were treated with triptolide by oral administration (gastric infusion; 0, 100, 200, 400 µg/kg) once daily for 8 weeks. At the end of the treatment, the concentrations of triptolide in blood and testis samples were analyzed with liquid chromatography/mass spectrometry (LC/MS) to obtain the toxicokinetic parameters. Triptolide showed a non-linear kinetics profile and was rapidly absorbed but relatively slowly eliminated in the rats. Specifically, an accumulation of triptolide was seen in the testis. In the hematological study, mean corpuscular hemoglobin concentration (MCHC) had a marginal decrease in all triptolide treated groups. Alkaline phosphatase (ALP) in serum increased significantly only in the 400 µg/kg group during clinical chemistry assays although no histopathological change was found in the hematopoietic system or liver. In the male reproductive toxicity studies, the testis and epididymis weights of all triptolide treatment groups decreased significantly. The cauda epididymis sperm content and motility even decreased to zero. Evident changes were observed in the seminiferous tubules and the epididymides of triptolide treated rats (e.g., intraepithelial vacuoles of varying sizes; increased germ cells degeneration, exfoliation and tubular atrophy). These findings provide valuable information to estimate the reproductive risk of triptolide in humans.