GM1 ganglioside induced myocardial restoration and survival of mice with experimental Chagas' disease.
In a previous work, our group reported that Albino Swiss male mice inoculated with T. cruzi to develop acute lethal infection by day 15 decreased parasitemia and survived when treated with total brain gangliosides (GT; 1 mg, daily). In this paper, GT were replaced by GM1 in 0.1 mg dose that caused diminished parasitemia from day 15 to 30 and survival of 80% by day 120 p.i. Treatment with GT 0.15 mg was ineffective. This indicates that GT effect was due to GM1 and that more sialyl residues on the same lipid moiety produces adverse results. GM1 was compared to other sialylated molecules: fetuine and colominic acid. Both of them increased parasitemias and death by day 16 p.i., suggesting that sialic residues favor parasite replication. Asialo-GM1 (0.1 mg daily) was also adverse. This pointed to GM1 not to other ganglioside or sphingolipid or sialoprotein as the active agent. Gangliosides are [Ca+2]i modulators, so GM1 was compared to nifedipine which blocks calcium channels only in the host. Nifedipine treated mice behaved as controls. It is proposed that if GM1 calcium modulation is involved it must be on the parasite rather than on the host. Electrocardiographic (ECG) records show that while infected mice die with bradycardia, treated mice survive and recover normal frequency. Uninfected treated mice showed no electrocardiographic alterations.
Cossy Isasi
S
S
Cátedra de Quimica Biologica, Facultad de Ciencias Medicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Argentina. scossy@biomed.fcm.unc.edu.ar
Fernandez
A R
AR
Paglini
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P
Bronia
D H
DH
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology; D004562:Electrocardiography; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000469:parasitology / Q000502:physiology*; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology
D002121:Calcium Channel Blockers; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D009543:Nifedipine