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Unveiling Lovastatin's Anti-Inflammatory Potential in Mouse's Brain during Acute Trypanosoma cruzi Infection
Beatriz Matheus de Souza Gonzaga1, Líndice Mitie Nisimura1, Laura Lacerda Coelho1
1Laboratório de Inovações Em Terapias, Ensino E Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil.
Biology
|May 24, 2024
Summary
Lovastatin did not improve brain microcirculation in experimental Chagas disease (CD). However, this statin showed anti-inflammatory effects by reducing certain immune cells and markers in the brain during acute infection.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Chagas disease (CD) can cause neurological complications like meningoencephalitis and stroke, often linked to cerebral microvasculopathy.
- Current CD treatments (benznidazole, nifurtimox) have limited chronic phase efficacy and significant side effects, necessitating new therapeutic strategies.
- Statins, like lovastatin, possess pleiotropic effects including anti-inflammatory and endothelial-protective properties, suggesting potential for treating CD-related brain issues.
Purpose of the Study:
- To investigate the therapeutic potential of lovastatin (LOV) in mitigating brain microvasculopathy and inflammation during acute Chagas disease (CD) infection.
- To evaluate LOV's impact on cerebral microcirculation, immune cell infiltration, and inflammatory markers in a mouse model of experimental CD.
- To determine if LOV exhibits trypanocidal activity or affects parasite load in the context of acute infection.
Main Methods:
- Swiss Webster mice were infected with the Y strain of *Trypanosoma cruzi*.
- Lovastatin (20 mg/kg/day) was administered intraperitoneally for 14 days, starting 24 hours post-infection.
- Analysis included parasitemia, cerebral blood flow, capillary density, leukocyte-endothelial interactions, and brain expression of inflammatory markers (CD3+, F4/80+, eNOS, VCAM-1, MCP-1, ICAM-1).
Main Results:
- Lovastatin treatment did not alter parasitemia, cerebral microcirculation, or reduce cerebral blood flow in *T. cruzi*-infected mice.
- LOV did not prevent increased CD3+ T-cells or eNOS levels in the infected brain.
- LOV administration prevented the increase in F4/80+ macrophages and ICAM-1 levels, suggesting an anti-inflammatory effect, while VCAM-1 and MCP-1 remained unchanged.
Conclusions:
- Lovastatin does not appear to directly improve cerebral microcirculation or reduce parasite load in acute experimental Chagas disease.
- LOV demonstrated a partial anti-inflammatory effect by modulating specific immune cell populations and adhesion molecules in the infected brain.
- Further research is required to fully elucidate the role and potential benefits of lovastatin in managing neurological complications of Chagas disease.

