Effects of cyclopiazonic acid and aflatoxin B1 on arachidonic acid metabolism, calcium mobilization and ultrastructure in rabbit platelet aggregation

Cyclopiazonic acid 및 aflatoxin B1이 토끼의 혈소판에서 arachidonic acid 대사, 칼슘 동원 및 초미세구조에 미치는 영향

  • Hong, Choong-man (Division of Hematopathology, Toxicological Research Institute, Korean FDA) ;
  • Jang, Dong-deuk (Division of Hematopathology, Toxicological Research Institute, Korean FDA) ;
  • Cho, Myung-haing (Department of Toxicology, College of Veterinary Medicine, Seoul National University)
  • 홍충만 (식품의약품안전본부 독성연구소 혈액병리과) ;
  • 장동덕 (식품의약품안전본부 독성연구소 혈액병리과) ;
  • 조명행 (서울대학교 수의과대학)
  • Received : 1996.07.10
  • Published : 1996.12.25


For better understanding the interrelationship of hemorrhage and aggregation mechanism, cyclopiazonic acid(CPA) known as promoting the aggregation of platelet, aflatoxin $B_1(AFB_1)$ inhibiting platelet aggregation were used as toxic mycotoxins in these studies. In order to investigate the potential role of prostaglandin metabolism on the platelet aggregation, a variety of prostaglandin metabolites such as $PGF_{2{\alpha}}$, $PGE_2$ and $TXB_2$ were measured in homogenized rabbit platelets by TLC and LSC. And the role of $Ca^{{+}{+}}$ on the platelet aggregation was investigated by flow cytometer. Finally, the morphological effects of mycotoxins on platelet were determined by transmission electron microscope. The results and conclusions obtained from these studies are: 1) CPA induced no changes but $AFB_1$ increased $PGE_2$ and $TXB_2$. 2) CPA promoted ADP, collagen, thrombin, A.A., and PAF-induced $Ca^{{+}{+}}$ release. $AFB_1$, however, decreased $Ca^{{+}{+}}$ level except collagen-induced $Ca^{{+}{+}}$ release. When the calcium blocker, verapamil, was used, CPA decreased thrombin-induced $Ca^{{+}{+}}$ release and increased collagen, ADP, PAF and A.A.-induced $Ca^{{+}{+}}$ release. $AFB_1$ in contrast decreased the all factors induced $Ca^{{+}{+}}$ release. 3) $AFB_1$ did not induce any ultrastructural changes except large vacuole formation in a few platelets. And CPA also did not induce any changes except moderate shape change, indicator of platelet activation. In conclusion, CPA promoted platelet aggregation by the increases of $Ca^{{+}{+}}$ release but had no changes in A.A. metabolites. Antiaggregating effects of $AFB_1$ may be due to decreases of $Ca^{{+}{+}}$ release and increases of $PGE_2$ and $PGF_{2{\alpha}}$ formation. These data provide the basis for the future study of mobilization and function of $Ca^{{+}{+}}$ in platelet aggregation.