Oxidative Stress and Survival of <i>Leishmania</i> spp.: A Relationship of Inverse Proportionality for Disease Outcome

Abstract

Abstract The development of oxidative stress depends on the deregulation of the fine balance between the proportion of reactive oxygen species (ROS) generation and the activity of antioxidants. As oxidative stress is deleterious for Leishmania sp., their host cell generates ROS as one of the foremost defence strategies. The parasites have also raised a variety of counteracting tricks in order to conquer this challenge. Upon infection, the host’s own antioxidant system is activated by the parasite to neutralise the oxidative stress-mediated protection. In addition to using the host’s antioxidant mechanisms, some genes within the parasite also make them more tolerant against oxidative stress. Therefore, the present review focuses on some major regulators intimately related to the equilibrium between oxidation and antioxidation following infection with Leishmania sp., which may be helpful in developing a comprehensive knowledge of this specific wing of infection biology associated with oxidative stress. Search Results Reactive oxygen species (ROS) play a dual role in leishmaniasis by contributing to both host defence and parasite survival mechanisms. In the host, ROS promote parasite clearance through induction of apoptosis, activation of pro-inflammatory signalling pathways (e.g., MAPK, JNK), inflammasome assembly, and M1 macrophage polarisation. Conversely, Leishmania species have evolved multiple strategies to neutralize ROS, including the upregulation of host antioxidant enzymes like HO-1, inhibition of ROS-producing pathways, and expression of parasite-derived antioxidants such as SOD, GPx, and trypanothione reductase. The parasite alsoadapts through gene regulation and metabolic changes to counter oxidative stress. Importantly, ROS have emerged as key targets for antileishmanial therapies, with various drugs and natural compounds shown to induce ROS-mediated parasite death, highlighting their potential in future therapeutic development. Conclusions In summary, the survival of Leishmania hinges on its ability to counteract host-induced oxidative stress. Targeting its antioxidant defences and enhancing host ROS production can disrupt this balance, leading to parasite death. Exploring ROS-related signalling offers a promising path for developing effective therapies against leishmaniasis.

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