Efficacy of albendazole-GM6001 co-therapy against Angiostrongylus cantonensis-induced meningitis in BALB/c mice.
Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole kills the nematode larvae staying in the brain. However, the dead larvae are capable of evoking a severe inflammatory response resulting in the brain damage. Matrix metalloproteinase 9 (MMP-9) is associated with the development of meningitis and with the immune inflammatory reaction. Presently, we studied the combination effects of albendazole and GM6001 (a MMP-9 inhibitor) against angiostrongyliasis in BALB/c mice. Co-administration of drugs produced marked effects; to kill the infecting larvae and to block MMP-9 activity. The combination treatment reduced MMP-9 activity by 89.2% in cerebrospinal fluid. The numbers of inflammatory cells increased significantly upon establishment of infection, but subsided upon co-treatment. Significantly fewer larvae were recovered from treated mice than from untreated, infected mice. The present results strongly suggest that co-therapy with albendazole and GM6001 may be an useful approach for the treatment of human angiostrongyliasis.
Lai
S C
SC
Department of Parasitology, Chung Shan Medical University, 110 Section 1, Chien-Kuo North Road, Taichung 402, Taiwan.
Jiang
S T
ST
Chen
K M
KM
Hsu
J D
JD
Shyu
L Y
LY
Lee
H H
HH
D015766:Albendazole / Q000008:administration & dosage / Q000627:therapeutic use*; D017185:Angiostrongylus cantonensis / Q000187:drug effects* / Q000472:pathogenicity; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D004338:Drug Combinations; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid; D061965:Matrix Metalloproteinase Inhibitors; D008581:Meningitis / Q000188:drug therapy* / Q000209:etiology / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017206:Strongylida Infections / Q000150:complications / Q000188:drug therapy*
D000871:Anthelmintics; D004338:Drug Combinations; D061965:Matrix Metalloproteinase Inhibitors; D020780:Matrix Metalloproteinase 9; D015766:Albendazole