Continuous administration of recombinant human endostatin (Endostar): A pre-clinical safety study
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- Published online on: March 30, 2012 https://doi.org/10.3892/etm.2012.534
- Pages: 1018-1022
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Abstract
The aim of this study was to evaluate the safety of the continuous administration of recombinant human endostatin (Endostar) in healthy mice. A total of 16 nude mice were randomly divided into four treatment groups: a continuous administration group injected intraperitoneally (i.p.) with 14 mg/kg Endostar over seven days, an intermittent administration group injected i.p. with 2 mg/kg Endostar daily for seven days, a saline injection group and an untreated control group. All mice were implanted with an intraperitoneal mini-osmotic drug pump filled with Endostar or saline. The serum concentration of Endostar, the cell fraction of CD11b-CD146+CD105+ vascular endothelial cells in the peripheral blood, the injury of the myocardial, lung and kidney tissues and the density of microvessels within these organs were observed 24 h after the termination of drug or saline administration. Only trace amounts of Endostar were detected in the serum of the continuous administration and intermittent administration groups. Myocardial, lung and kidney tissues exhibited no detectable signs of injury and no differences in the density of microvessels were found in these organs among the four groups. Yet, the cell fraction (in %) of CD11b-CD146+CD105+ vascular endothelial cells in the peripheral blood was higher in the continuous administration group compared with that in the other treatment groups (P=0.011). This suggests that intermittent Endostar delivery did not significantly impact the vascular endothelium, while continuous Endostar administration may promote injury of the endothelium. In conclusion, the continuous administration of Endostar does not appear to be a safe method by which to administer this antiangiogenic agent to healthy nude mice.
