Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi, affects several million people in Latin America and is currently found in non-endemic areas such as Spain. It presents an acute phase, for which there is pharmacological treatment, although with strong side effects. The chronic phase of the disease is usually asymptomatic for decades; but then, in about 30% of cases, chronic Chagasic cardiomyopathy develops.
In a study published in the journal PLOS Neglected Tropical Diseases , researchers from the Center for Molecular Biology (CBMSO) of the Autonomous University of Madrid (UAM) discovered in mice that during T. cruzi infection a decrease in L-arginine (L-arg) levels occurs, produced by the overexpression of the arginase 1 enzyme (Arg1) in myeloid suppressor cells (MDSCs). In addition, they identified that the infiltration and expansion of these cells in the heart during infection is associated with the susceptibility of the infection.
L-arg is a substrate of an enzyme called inducible nitric oxide synthase (iNOS), also increased in MDSCs. The iNOS converts the L-arg into citrulline and nitric oxide (NO), the latter is necessary to eliminate the parasite.
On the other hand, the researchers observed that the infection produces an increase in asymmetric dimethylarginine (ADMA), as a result of protein catabolism with arginine residues. ADMA is an inhibitor of iNOS, so even though the expression of iNOS increases because of the infection, the inhibited enzyme is not able to produce sufficient NO. This, in addition with the lack of L-arg, inhibits the production of NO, which is necessary to control the infection.
Heart disease marker
It is noteworthy that the low L-arg/ADMA ratio is considered a marker of heart disease in other cardiomyopathies. “The intake of supplement of L-arginine produced a beneficial effect, drastically reducing the number of parasites and preventing the death of the mice by the infection. In addition, cardiac function altered in the infected mice also improved with the L-arginine supplement,” the researchers say.
“The relevance of our results lies in the fact that, on the one hand, the levels of L-arginine/ADMA could be predictive markers of chagasic cardiomyopathy. And on the other, as L-arginine is a commonly used food supplement, it could be useful as adjunct treatment of acute infections, administered as a complement to the usual medication; and it could even allow reducing the dose of the drug in order to avoid the strong side effects,” they detail.
The work was carried out by the groups of Manuel Fresno and Núria Gironès of the CBMSO, in collaboration with the group of Susana Gea of the Center for Research in Biochemistry and Immunology of the National Council of Scientific and Technological Research (CIBICI-CONICET) of Córdoba (Argentina), and the group of Héctor Omar Rodríguez-Angulo of the Venezuelan Institute of Scientific Investigations (IVIC), in Caracas (Venezuela).