Superoxide dismutase activity in patients of cerebral malaria

Raza, Adil; Varshney, Sumit; Khan, Haris M.; Malik, Mohammad Bilal; Mehdi, Abbas Ali; Shukla, Indu

doi:10.1016/s2222-1808(15)60856-8

Cited by 13 publications

(7 citation statements)

References 18 publications

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“…In addition, all of these chalcones can chelate iron cations in heme that would otherwise be consumed by Plasmodium parasites and enhance their replication [17,20]. Butein as an antioxidant catechol compound can also contribute to better scavenging of superoxide radicals that are toxic to the host cells and utilized by Plasmodium parasites [44] as shown here by RRDE and DFT results. In conclusion, our findings provide more evidence for the use of chalcones 1-4 as starting points for the development of novel, effective, and affordable antimalarial drugs.…”

Section: Discussionmentioning

confidence: 56%

X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

Okoye

Caruso

et al. 2021

Molecules

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Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in E. abyssinica, have shown moderate antiplasmodial activity. Here, we describe results from experimental and computational investigations of four structurally related chalcones, butein, 2′,4′-dihydroxy-3,4-dimethoxychalcone (DHDM), homobutein and 5-prenylbutein to elucidate possible molecular mechanisms by which these compounds clear malaria parasites. The crystal structures of butein and DHDM show that butein engages in more hydrogen bonding and consequently, more intermolecular interactions than DHDM. Rotating ring-disk electrode (RRDE) voltammetry results show that butein has a higher antioxidant activity towards the superoxide radical anion compared to DHDM. Computational docking experiments were conducted to examine the inhibitory potential of all four compounds on falcipain-2, a cysteine protease that is involved in the degradation of hemoglobin in plasmodium-infected red blood cells of the host. Overall, this work suggests butein as a better antimalarial compound due to its structural features which allow it to have greater intermolecular interactions, higher antioxidant activity and to create a covalent complex at the active site of falcipain-2.

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Section: Discussionmentioning

confidence: 56%

X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

Okoye

Caruso

et al. 2021

Molecules

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“…Decreased SOD activity was also found in the plasma of patients infected with Plasmodium vivax, and was associated with the intensity of the infection [29]. Raza et al [30] reported a negative correlation between SOD activity and parasitic activity in patients with subtropical cerebral malaria. Finally, it was found that decreased activity of SOD reduces host responses to oxidative stress caused by inflammatory processes [31].…”

Section: Discussionmentioning

confidence: 97%

Antioxidant defense in the eyes of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp.

et al. 2020

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Background: Acanthamoeba spp. are ubiquitous pathogens which cause granulomatous amoebic encephalitis and disseminated infection. Moreover, Acanthamoeba spp. infection of the cornea leads to Acanthamoeba keratitis. Our previous study showed that the infection of an eyeball may also take place via the migration of trophozoites through the optic nerve from the brain to the eyes. The aim of the study was to analyze the activity of enzymatic antioxidants and the concentration of non-enzymatic antioxidant in the eyes of immunocompetent and immunocompromised mice with disseminated acanthamoebiasis. Results: In the immunocompetent mice infected with Acanthamoeba spp. we noted a significant decrease in catalase activity at 8 and 16 days post-infection (dpi). Glutathione reductase activity was significantly lower at 16 dpi compared to the control group and glutathione concentration was statistically higher at 24 dpi than in the control group. In the immunosuppressed mice, a statistically significant increase in glutathione concentration in the eye samples was found at 16 dpi compared to those not infected with Acanthamoeba spp. In the immunosuppressed mice infected with Acanthamoeba spp., glutathione peroxidase activity was statistically lower at 8 dpi, and glutathione concentration was statistically significantly higher at 16 dpi compared to the control group. Conclusions: The inflammatory response in the eyes of hosts with experimental acanthamoebiasis led to changes in the activity of enzymatic antioxidants and the content of non-enzymatic antioxidant. Therefore, the dysregulation of antioxidants may play a role in the pathomechanism of Acanthamoeba eye infection.

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“…Importantly, malaria patients have been reported to have lower catalase activity than healthy controls, but a higher SOD activity, thus resulting in the accumulation of H 2 O 2 . Moreover, free heme released from the hemoglobin of ruptured parasite infected red cells may continuously undergo autoxidation, producing superoxide, which dismutates into H 2 O 2 and is a potential source for subsequent oxidative reactions in endothelial cells [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Pore Forming Proteins of Plasmodium Triggers the Necrosis of Endothelial Cells Attributed to Malaria Severity

Shivappagowdar

Garg

Srivastav

et al. 2021

Toxins

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Severe malaria caused by Plasmodium falciparum poses a major global health problem with high morbidity and mortality. P. falciparum harbors a family of pore-forming proteins (PFPs), known as perforin like proteins (PLPs), which are structurally equivalent to prokaryotic PFPs. These PLPs are secreted from the parasites and, they contribute to disease pathogenesis by interacting with host cells. The severe malaria pathogenesis is associated with the dysfunction of various barrier cells, including endothelial cells (EC). Several factors, including PLPs secreted by parasites, contribute to the host cell dysfunction. Herein, we have tested the hypothesis that PLPs mediate dysfunction of barrier cells and might have a role in disease pathogenesis. We analyzed various dysfunctions in barrier cells following rPLP2 exposure and demonstrate that it causes an increase in intracellular Ca2+ levels. Additionally, rPLP2 exposed barrier cells displayed features of cell death, including Annexin/PI positivity, depolarized the mitochondrial membrane potential, and ROS generation. We have further performed the time-lapse video microscopy of barrier cells and found that the treatment of rPLP2 triggers their membrane blebbing. The cytoplasmic localization of HMGB1, a marker of necrosis, further confirmed the necrotic type of cell death. This study highlights the role of parasite factor PLP in endothelial dysfunction and provides a rationale for the design of adjunct therapies against severe malaria.

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Superoxide dismutase activity in patients of cerebral malaria

Cited by 13 publications

References 18 publications

X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

Antioxidant defense in the eyes of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp.

Pathogenic Pore Forming Proteins of Plasmodium Triggers the Necrosis of Endothelial Cells Attributed to Malaria Severity

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