Glycine Supplementation Reduces Lesion Size and Parasite Burden in BALB/c Mice Infected with Leishmania mexicana

Glycine, a non-essential amino acid, plays diverse biological roles, including antimicrobial and anti-inflammatory activities, cytoprotective effects, neurotransmitter functions, and potential anticancer properties. The potential of glycine supplementation in parasitic diseases, such as leishmaniasis, remains underexplored. Leishmania mexicana, a protozoan parasite, is a causative agent of cutaneous leishmaniasis, characterized by chronic lesions and significant immunopathology. This study investigates the impact of glycine supplementation on disease progression and parasite control in a BALB/c mouse model of L. mexicana infection. BALB/c mice were infected with L. mexicana and received glycine-supplemented drinking water ad libitum, beginning on the day of infection. Glycine supplementation exhibited a protective effect, as evidenced by significantly reduced lesion sizes and decreased parasite burdens. Cytokine profiling of spleen cells from glycine-treated mice revealed an immunomodulatory effect, characterized by increased interleukin-10 (IL-10) production and decreased tumor necrosis factor-alpha (TNF-α) levels upon stimulation with L. mexicana promastigote antigens. In vitro studies showed that glycine supplementation inhibited promastigote and amastigote growth in a dose-dependent manner. Macrophages cultured in glycine-enriched media showed reduced parasite recovery from infected macrophages. Importantly, no cytotoxic effects were observed in cultured host cells. Histological analysis of tissue lesions showed a lower parasite burden and diminished inflammatory infiltrate in glycine-treated mice. The histological analysis of liver and kidney tissues from glycine-supplemented mice showed no detectable histopathological alterations in liver or kidney at the tested doses. These findings suggest that glycine may represent a promising anti-Leishmania agent for controlling disease progression. Glycine’s dual ability to modulate host immune responses and directly inhibit parasite growth highlights the potential benefits of early glycine supplementation in cutaneous leishmaniasis.