Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis With Features That Overlap With Anemia of Chronic Disease

Lakkavaram, Asha; Lundie, Rachel J.; Hang, Đo Thi Thu; Ward, Alister C.; Koning-Ward, Tania F de

doi:10.3389/fmicb.2020.00702

Cited by 15 publications

(13 citation statements)

References 80 publications

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“…The changes in parasitaemia induced by the inoculation of P. berghei are consistent with the results of previous investigators [ 31 , 32 ]. As presented in Table 2 and Additional file 1 : Figure S1, evident increases ( p < 0.05) in percentage parasitaemia in control (untreated inoculated mice) were noticed on day 4 (14.40 ± 0.45) and day 5 (16.37 ± 1.25) post-inoculation compared with 9.40 ± 1.23 for day 3.…”

Section: Resultssupporting

confidence: 92%

“…Changes in the haematological profile are a consistent feature in malaria parasitaemia and represent a basic malaria infection pattern. In the control group, the observed decrease in blood parameters corroborates with previous reports documenting haematological indices of malaria-infected patients [34,35] and increased RBCs breakdowns in P. berghei-infected mice, thus resulting in anaemia [32]. In marked contrast to the control, amounts of WBC, RBC, Hb and PCV in PHCSBD-treated groups were significantly (p < 0.05) higher (Table 4).…”

Section: Resultssupporting

confidence: 89%

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Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives

Ibezim

Ofokansi

Ndukwe

et al. 2022

Malar J

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Background The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property. Methods Here, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques. Results The two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor. Conclusion This study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 89%

Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives

Ibezim

Ofokansi

Ndukwe

et al. 2022

Malar J

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“…Inflammation from severe tissue damage or infection (e.g. bacterial or parasitic) can impede the erythropoietin (EPO) response in bone marrow, suppressing erythroid progenitor cells (EPCs) and increasing EPCs in the peripheral blood after severe injury 1,2 ; however, splenic erythropoiesis is initiated to produce new erythrocytes to compensate for the anemia. Similarly, tissue hypoxia resulting from disease and injury, 3,4 high altitude (hypobaric hypoxia (HB)) exposure, 5 or severe hemorrhage (i.e.…”

Section: Introductionmentioning

confidence: 99%

Mild hypobaric hypoxia influences splenic proliferation during the later phase of stress erythropoiesis

Zhang

Patel

Soulakova

et al. 2021

Exp Biol Med (Maywood)

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Tissue trauma and hemorrhagic shock are common battlefield injuries that can induce hypoxia, inflammation, and/or anemia. Inflammation and hypoxia can initiate adaptive mechanisms, such as stress erythropoiesis in the spleen, to produce red blood cells and restore the oxygen supply. In a military context, mild hypobaric hypoxia—part of the environmental milieu during aeromedical evacuation or en route care—may influence adaptive mechanisms, such as stress erythropoiesis, and host defense. In the present study, healthy (control), muscle trauma, and polytrauma (muscle trauma and hemorrhagic shock) mice were exposed to normobaric normoxia or hypobaric hypoxia for ∼17.5 h to test the hypothesis that hypobaric hypoxia exposure influences splenic erythropoiesis and splenic inflammation after polytrauma. This hypothesis was partially supported. The polytrauma + hypobaric hypoxia group exhibited more splenic neutrophils, fewer total spleen cells, and fewer splenic proliferating cells than the polytrauma+normobaric normoxia group; however, no splenic erythroid cell differences were detected between the two polytrauma groups. We also compared splenic erythropoiesis and myeloid cell numbers among control, muscle trauma, and polytrauma groups. More reticulocytes at 1.7 days (40 h) post-trauma (dpt) and neutrophils at 4 dpt were produced in the muscle trauma mice than corresponding control mice. In contrast to muscle trauma, polytrauma led to a reduced red blood cell count and elevated serum erythropoietin levels at 1.7 dpt. There were more erythroid subsets and apoptotic reticulocytes in the polytrauma mice than muscle trauma mice at 4 and 8 dpt. At 14 dpt, the red blood cell count of the polytrauma + normobaric normoxia mice was 12% lower than that of the control + normobaric normoxia mice; however, no difference was observed between polytrauma + hypobaric hypoxia and control + hypobaric hypoxia mice. Our findings suggest muscle trauma alone induces stress erythropoiesis; in a polytrauma model, hypobaric hypoxia exposure may result in the dysregulation of splenic cells, requiring a treatment plan to ensure adequate immune functioning.

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“…In separate studies, [16,17] associated diminution in body weight to the loss of appetite, reduced metabolism, altered gut function, hypoglycemia and most importantly massive destruction of erythrocytes. In addition, P. berghei infected rats (19) and L .donovani infected mice (20) studies reported high anemia which was due to the destruction of erythrocytes and splenocytes respectively.…”

Section: Discussionmentioning

confidence: 99%

Concomitant infection withLeishmania donovaniandPlasmodium berghei altersclinical and immune responses in BALB/c mice

Mutiso

Macharia

et al. 2021

Preprint

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Malaria and visceral leishmaniasis coexist in the same geographical regions. However, dual co-infection with parasites causing these diseases and their impact on public health is poorly documented. Interactions between these parasites may play a role in disease outcome. The present study set out to evaluate the clinical and immunological parameters following Leishmania donovani and Plasmodium berghei co-infection in BALB/c mice. Mice were divided into four groups; L. donovani- only, L. donovani- P. berghei , P. berghei- only and naïve. Body weight, parasite burden, total IgG, IFN-γ and IL-4 responses were determined. To determine the survival rate, four mice were used from each group. Tissues for histological analysis were taken from spleen, liver and brain. Results indicated significant differences in body weight (P<0.0001), L. donovani parasite load (P< 0.0001 ), L. donovani IgG (P< 0.0001), P. berghei parasitemia (P= 0.0222), P. berghei IgG (P= 0.002), IFN-γ (P<0.0001) and IL-4 (P<0.0001) in dual-infected mice. There was no correlation between L. donovani parasite load and IgG responses in single or dual infections, while there was a positive relationship of P. berghei parasitemia and IgG responses in the dual infection group only. Plasmodium berghei had the highest mortality rate compared to L. donovani - only and L. donovani- P. berghei infected mice groups. Histological analyses showed enlarged red and white pulps and pathological changes in the spleen, liver and brain tissues which were less pronounced in co-infected group. We conclude that L. donovani and P. berghei co-infection reduces disease severity and these changes seem to correlate with variation in serum IgG and cytokines (IFN-γ and IL-4). Therefore, the study recommends the importance of inclusion of early screening of malaria in Visceral Leishmaniasis patients in regions where malaria is co- endemic.

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Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis With Features That Overlap With Anemia of Chronic Disease

Cited by 15 publications

References 80 publications

Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives

Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives

Mild hypobaric hypoxia influences splenic proliferation during the later phase of stress erythropoiesis

Concomitant infection withLeishmania donovaniandPlasmodium berghei altersclinical and immune responses in BALB/c mice

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