Diseases · Published 2026-07-03 · DOI 10.3390/diseases14070240
Background/Objectives: The coccidian protozoan <i>Toxoplasma gondii</i> (<i>T. gondii</i>) is among the most prevalent zoonotic parasites worldwide. Nitric oxide (NO) production by macrophages is considered a critical microbicidal mechanism against various intracellular pathogens, including <i>T. gondii</i>. While the role of the inducible nitric oxide synthase isoenzyme (iNOS) has been widely investigated in both acute and chronic <i>T. gondii</i> infections, the specific functions of the neuronal (nNOS) isotype in the antiparasitic immune response, particularly during chronic toxoplasmosis, remain largely uncovered. Hence, this report seeks to bridge the gap regarding the potential participation of nNOS in experimental chronic <i>T. gondii</i> infection. Methods: The study included 56 Swiss albino mice, equally allocated into four experimental groups: (G1) negative control, (G2) infected control, (G3) infected-L-arginine-treated, and (G4) infected-7-Nitroindazole-treated. All groups except (G1) were orally infected with the avirulent (ME49) <i>T. gondii</i> strain. Nine weeks post-infection, all mice were euthanized for parasitological, histopathological, immunohistochemical, and biochemical analyses. Results: The NO donor, L-arginine, induced a significant reduction in the number of <i>T. gondii</i> cysts, together with strong nNOS immunoreactivity in the brain sections of the treated mice. Conversely, the highest parasitic burden was observed following selective nNOS inhibition with 7-Nitroindazole, exacerbating parasite-induced pathology. Conclusions: The neuronal isotype serves as a critical source of NO production during the chronic stage of <i>T. gondii</i> infection, thereby enhancing parasite elimination and contributing to host tissue protection.
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Omar, M. (2026). From Insight to Impact: Spotlight on the Potential Implications of the Neuronal Nitric Oxide Synthase Isoenzyme (nNOS) in Experimental Chronic Toxoplasmosis. Diseases. https://doi.org/10.3390/diseases14070240