Acute toxicity and genotoxicity evaluations of Nattokinase, a promising agent for cardiovascular diseases prevention.

Cardiovascular diseases (CVDs) are the leading cause of death in the world; however, current agents for CVDs prevention are still limited. Owing to the serious bleeding risk of Aspirin, FDA recently recommended against it from preventing first heart attacks. Nattokinase (NK), a serine protease possessing many key beneficial effects on cardiovascular system, is being pursued as a promising alternative agent. In light of this, the safety profile of NK, in particular its potential genotoxicity, need to be characterized. The present study is therefore aimed to evaluate the toxicological profile of NK. To assess acute safety, mice were orally administrated with NK at its maximum concentration and the maximum feeding volume twice in a single day, no mortality or toxicological signs were observed. Hence, the maximum daily tolerant dose of NK in mice is up to 480000 FU/kg, which is 1000 times more compared to the recommended daily dose for human. In the genotoxicity studies, NK showed no mutagenic activity as tested by both Ames test and in vivo micronucleus assay. Moreover, NK demonstrated no evidence of potential to induce chromosome aberrations in CHL cells. These results indicate that there is no safety concern for NK in the present preclinical safety studies, supporting the safety of NK as an agent for CVDs prevention.