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Acute and subacute toxicity studies on triptolide and triptolide-loaded polymeric micelles following intravenous administration in rodents

Acute and subacute toxicity studies on triptolide and triptolide-loaded polymeric micelles following intravenous administration in rodents

Authors :
Lingyun Xu
Huibi Xu
Yinsheng Qiu
Xiangliang Yang
Waikei Lam
Wuliji Ao
Source :
Food and Chemical Toxicology. 57:371-379
Publication Year :
2013
Publisher :
Elsevier BV, 2013.

Abstract

Except its anti-tumour effects, triptolide (TP) also shows multiple pharmacological side activities, such as immune-suppressive and male anti-fertility. To increase the therapeutic index of TP, a novel polymeric micelle system containing TP (TP-PM) has been developed to treat tumour. Our previous studies have demonstrated the good anti-tumour efficacy of TP-PM. This paper investigated the acute toxicity in mice and subacute toxicity in rats of TP-PM and TP. Results demonstrated that the LD50 for TP-PM and TP administered intravenously were 1.06 mg/kg and 0.83 mg/kg in mice, respectively. In subacute toxicity study, TP-PM and TP were administered intravenously at the dose levels of 0.1 mg/kg and 0.3 mg/kg for 14 d. Compared to the control, there was significant decrease in the serum AST activities, the testis ACP activities, thymus index, testis index, and significant increase in spleen index, and obvious histopathological changes in rats treated with TP, however, the toxicities of TP-PM on liver, kidney, testis and spleen are slighter than TP. Compared to TP, TP-PM significantly increased the ACP activity of the testis and decreased the MDA level in serum. So, the polymeric micelles may be a novel drug delivery carrier of TP for reducing the toxicities of TP.

Details

ISSN :
02786915
Volume :
57
Database :
OpenAIRE
Journal :
Food and Chemical Toxicology
Accession number :
edsair.doi.dedup.....c21474a147008c521c9dde41f521b359
Full Text :
https://doi.org/10.1016/j.fct.2013.03.044