Studies on anti-malarial activity of gramicidin
Grant-in-Aid for Scientific Research (C).
|Research Institution||Nagoya University|
KAWAMOTO Fumihiko Nagoya University School of Medicine, 医学部, 講師 (40115556)
|Project Fiscal Year
1992 – 1993
Completed(Fiscal Year 1993)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1993 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1992 : ¥1,000,000 (Direct Cost : ¥1,000,000)
|Keywords||Gramicidin D / Antibiotic / Anti-malaria activity / Hemolysis / Malaria parasite / Plasmodium falciparum / Malarial drug / Membrane protein / グラミシジンD / 抗生物質 / 抗マラリア作用 / 溶血作用 / マラリア原虫 / 熱帯熱マラリア / マラリア治療薬 / 膜蛋白 / グラミシジン / 溶血反応 / ネズミマラリア|
1. Hemolysis of malaria-infected erythrocytes gramicidin D
Hemolysis of P.berghei- and P.falciparum-infected erythrocytes by 1-10 muM gramicidin quickly occurred in a dose-response manner. On the contrary, hemolysis of Anormal erythrocytes treated with 10 muM gramicidin was not observed.
2. Effects of gramicidin D on the growth of P.berghei in vivo.
When infected mice with about 30% parasitaemia were administrated gramicidin D by daily injections into the peritoneal cavity from day 5 to day 9, or given intraperitoneal administration from day 0 to day 3 at the same time of infection, remarkable effectiveness for cure was observed.
3. Osmotic protection and morphological observation
The gramicidin D-induced hemolysis was protected by addition of polyethyleneglycol 4,000. This indicates that gramicidin D may produce bigger pore on the malaria-infected erythrocytes, and that the pore size produced may be, at least, bigger than 37A.It was apparent that the infected RBC lost hemoglobins from the cytosol, differing from non-infected RBCs. In addition, free prasites including trophozoites, schizonts and gametocytes escaped from RBCs were also seen. Unfortunately, however, any 'hole' on the membrane of the infected RBCs was not detected by electronmicroscopy.
4. Effects of gramicidin on P.falciparum
Treatment with 0.5-1 muM gramicidin strongly inhibited the asexual growth of P.falciparum in vitro. In P.falciparum-infected RBCs adhering to the surface of melanoma cells, these RBCs were broken or released from melanoma cells, indicating a possibility to use cure for severe malaria.
5. Investigation on the action mechanism of gramicidin D
A single protein of about 30kd was isolated from the p. berghei-infected erythrocytes by the batch method using gramicidin-conjugated Epoxy-activated Sepharose 6B.Molecular and biochemical properties of this protein is now being investigated.
Research Output (7results)