Study on the toxicity of the repeated administration of protective polypeptides in rats

ObjectiveTo evaluate the toxic reaction of human body protection peptide(HuBPP) in rat, and determine non-toxic reaction dose for clinical application and providing the reference information in clinical safe medication and monitoring of adverse reactions.

MethodsThe dosage of administration in 80 SD rats were confirmed by single intravenous and intramuscular injection.The dose of 0 mg/kg, 0.2 mg/kg, 1 mg/kg and 4 mg/kg were intramuscularly injected into the control group, low, medium high dose groups for 1 month, respectively(30 rats each group).The body weight and food intake in four groups were recorded during the test, the biochemical index at the end of drug administration and recovery period were detected, and the toxicity change of main organs was detected using histopathology.

ResultsThe acute toxicity test showed that there was no significant change in the observed indicators between control group and experiment group.The long-term toxicity test showed that there was no statistical significance in toxicity reaction of body weight, food intake and main organ indicators between control group and experiment group(P>0.05).After the long-term poison test, the levels of MCHC and MPV in male rats of high-dose group were higher and lower than that in control group, respectively(P < 0.01 and P < 0.05);the levels of TG and Na⁺ in female rats of middle-dose group were higher and lower than that in control group, respectively(P < 0.05);the levels of APTT in male rats of high- and middle-dose group were significantly lower than that in control group(P < 0.05);the Cl^- concentration in high-dose group was significantly higher than that in control group(P < 0.05).At the end of the recovery period, the values of RDW in male rats of high-dose group were lower than those in control group(P < 0.05), the levels of ALT, GLU, and TG in female rats of low-dose group were significantly higher than those in control group(P < 0.05 to P < 0.01).However, the parameters were within the normal range as reported in literature, and the significant difference of which was not found.

ConclusionsUnder the condition of the test, the 4 mg/kg or less than 4 mg/kg of HuBPP is safe dose in rats.