Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

Abstract

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

Keywords: Toxoplasma gondii; antioxidants; drugs; oxidative stress; pathogenic process; toxoplasmosis treatment.

Figure 1

The mechanisms of oxidative injury and antioxidant defense in the course of toxoplasmosis in the parasite and in the host. SOD, superoxide dismutase; GPx, glutathione peroxidase; TBARS, thiobarbituric acid reactive substances; GSH, reduced glutathione; MDA, malondialdehyde; CAT, catalase; NO, nitric oxide; Nox, NADPH–oxidase complex; GST, glutathione S-transferase; RNS, reactive nitrogen species; ROS, reactive oxygen species; TgIF2K-B, Toxoplasma gondii eukaryotic initiation factor 2 (eIF2α) kinase.

Figure 2

The chemical compounds that may affect the oxidant–antioxidant balance as promising novel anti-Toxoplasma therapeutics. ROS, reactive oxygen species; NO, nitric oxide.