Long-term toxicity of endostatin injection to Beagle dogs / 解放军医学杂志

ABSTRACT

Objective To evaluate the long-term toxicity of endostatin injection to Beagle dogs,and to provide safety evidence for clinical experiments.Methods Twenty-four pure-blood Beagle dogs were assigned to four groups averagely with six dogs for each group,and the sex ratio was 1∶1.The animals in three of four groups received endostatin injection at low(1.6mg/kg),medium(6.3mg/kg)and high(25.0mg/kg)dosage,respectively,and the animals in the other group acted as control.The Beagle dogs were injected intravenously daily for up to 3 months with the exception of the dogs in control group.The indicators of ordinary toxic response,weight,electrocardiogram and hematology were collected,and the blood biochemical analysis,routine urinalysis and histopathologic examination were also performed.Results Only ordinary toxic responses such as anorexia and laxness were observed from l dog in high dose group,and simultaneously disappeared in 4 days.The weight of all Beagle dogs studied increased in a normal rate.No significant difference was found in each group of dogs on heart rate,electrocardiogram and indicators of urinalysis.No evident changes were observed in dogs on hematological and biochemical indexes.The pathological chances in different levels were observed in a dog's liver of low dosage group and a dog's kidneys of blank control group,but such changes were regarded as the spontaneous pathological changes,not related to the application of endostatin injection.Conclusion The non-toxic dose of endostatin injection on Beagle dogs was estimated to be 6.3 mg/kg under the present conditions.