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 inoculat ed with T. cruzi to develop acute lethal infection by day 15 decreased para sitemia 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 d iminished 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 w as due to GM1 and that more sialyl residues on the same lipid moiety produc es adverse results. GM1 was compared to other sialylated molecules: fetuine and colominic acid. Both of them increased parasitemias and death by day 1 6 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 gangl ioside or sphingolipid or sialoprotein as the active agent. Gangliosides ar e [Ca+2](i) modulators, so GM1 was compared to nifedipine which blocks calc ium 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 th e parasite rather than on the host. Electrocardiographic (ECG) records show that while infected mice die with bradicardia, treated mice survive and re cover normal frequency. Uninfected treated mice showed no electrocardiograp hic alterations. (C) 1999 Elsevier Science B.V. All rights reserved.