Oxidative Stress and Pathogenesis in Malaria

Abstract

Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to Plasmodium infection. Moreover, host oxidative enzymes, such as xanthine oxidase, are upregulated in malaria patients. Although increased production of reactive oxygen species contributes to the clearance of the parasite, excessive amounts of these free radicals can mediate inflammation and cause extensive damage to host cells and tissues, probably contributing to severe pathologies. Plasmodium has a variety of antioxidant enzymes that allow it to survive amidst this oxidative onslaught. However, parasitic degradation of hemoglobin within the infected red blood cell generates free heme, which is released at the end of the replication cycle, further aggravating the oxidative burden on the host and possibly contributing to the severity of life-threatening malarial complications. Additionally, the highly inflammatory response to malaria contributes to exacerbate the oxidative response. In this review, we discuss host and parasite-derived sources of oxidative stress that may promote severe disease in P. falciparum infection. Therapeutics that restore and maintain oxidative balance in malaria patients may be useful in preventing lethal complications of this disease.

Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

“…Proinflammatory and immunoregulatory cytokines play important roles in shaping T-cell activation and adaptive immune responses ( Urban et al, 2005 ). Reactive oxygen species produced by phagocytic cells in response to parasites, and through cell-free heme released during hemolysis, contribute to inflammation and tissue damage ( Vasquez et al, 2021 ).…”

Caspase-4 and -5 Biology in the Pathogenesis of Inflammatory Bowel Disease

“…Heme is a DAMP released from red blood cells, whose excessive release due to hemolysis is a key feature of several disease states, including sepsis, malaria, and sickle cell disease. Higher levels of free heme have been implicated in inflammatory activation of macrophages, monocytes, and endothelial cells ( Larsen et al, 2010 ; Belcher et al, 2014 ; Vinchi et al, 2016 ; Bolívar et al, 2021 ; Vasquez et al, 2021 ). Bolívar et al proposed that this inflammatory signalling is in part mediated by the non-canonical inflammasome ( Bolívar et al, 2021 ).…”

Anti-malarial, anti-inflammatory and antioxidative activities of the aqueous extract of <em>Picralima nitida</em> (STAPF) TH. &amp;H. Durand fruits (Apocynaceae) in rats

“…The formation of free radicals linked with oxidative stress is often the cause of various systemic abnormalities in malaria, demonstrating the complex host-parasite connection. [25] . The generation of free radicals in malaria could be owing to the host's inflammatory response, as observed in this study, or to high levels of free iron, which catalyse Haber-Weiss and Fenton reactions [24] .…”