Long-term toxic effect of recombinant batroxobin on Macaca mulatta / 第二军医大学学报

ABSTRACT

Objective: To study the long-term (iv for 30 days) toxic effect of recombinant batroxobin (rBAT) on Macaca mulatta. Methods: Twenty-four Macaca mulatta (12 male and 12 female) were randomly divided into 4 groups according to their body weights (n=6) rBAT treatment groups (1.5, 5.0, 15.0 kU/kg of rBAT once daily for 30 consecutive days through iv injection) and acetate buffer treatment group (as control). Half of the animals in each group were sacrificed at the end of medication and the rest were sacrificed after another 15 days' recovery. The general symptoms, the hematological, chemical parameters, urinalysis values, ECG results, bone marrow findings, pathologic changes and the antibody detection were observed or performed in all groups. Results: On d15 and d30, the blood samples of each group were collected at 30 min and 24 h after iv injection. Compared with control group or with d0 data of each corresponding group, the fibrinogen (Fib) was significantly decreased 30 min after iv injection of rBAT, and the decrease was in a dose-dependent manner. Fib returned to the normal level 24 h after iv injection. Histopathological examination showed congestion and slight edema of liver and kidney cells in each group, probably due to latent infection of the animals. On d30, there was local inflammatory reaction in the injection sites of some animals in each group, but none was found on d45. Non-neutralizing antibodies to rBAT were continuously detected from d15 to d45. Conclusion: rBAT has pharma cological and toxicological effects on hematology system of Macaca mulatta. It can dose-dependently decrease Fib. The target organ of rBAT is the hematology system and the effect of rBAT is reversible. The safety dose of rBAT for Macaca mulatta is 1.5 kU/ kg. Attention should be given when rBAT is used clinically.