Lambda-carrageenan treatment exacerbates the severity of cerebral malaria caused by Plasmodium berghei ANKA in BALB/c mice

Abstract

BackgroundThere is an urgent need to develop and test novel compounds against malaria infection. Carrageenans, sulphated polysaccharides derived from seaweeds, have been previously shown to inhibit Plasmodium falciparum in vitro. However, they are inflammatory and alter the permeability of the blood–brain barrier, raising concerns that their use as a treatment for malaria could lead to cerebral malaria (CM), a severe complication of the disease. In this work, the authors look into the effects of the administration of λ-carrageenan to the development and severity of CM in BALB/c mice, a relatively non-susceptible model, during infection with the ANKA strain of Plasmodium berghei.MethodsFive-week-old female BALB/c mice were infected with P. berghei intraperitoneally. One group was treated with λ-carrageenan (PbCGN) following the 4-day suppressive test protocol, whereas the other group was not treated (PbN). Another group of healthy BALB/c mice was similarly given λ-carrageenan (CGN) for comparison. The following parameters were assessed: parasitaemia, clinical signs of CM, and mortality. Brain and other vital organs were collected and examined for gross and histopathological lesions. Evans blue dye assays were employed to assess blood–brain barrier integrity.ResultsPlasmodium berghei ANKA-infected BALB/c mice treated with λ-carrageenan died earlier than those that received no treatment. Histopathological examination revealed that intracerebral haemorrhages related to CM were present in both groups of infected BALB/c mice, but were more numerous in those treated with λ-carrageenan than in mock-treated animals. Inflammatory lesions were also observed only in the λ-carrageenan-treated mice. These observations are consistent with the clinical signs associated with CM, such as head tilt, convulsions, and coma, which were observed only in this group, and may account for the earlier death of the mice.ConclusionThe results of this study indicate that the administration of λ-carrageenan exacerbates the severe brain lesions and clinical signs associated with CM in BALB/c mice infected with P. berghei ANKA.

Factors influencing tissue cyst yield in a murine model of chronic toxoplasmosis

“…Direct brain/CNS involvement is noted in the case of a murine Plasmodium berghei study where it may be linked to intra-cerebral hemorrhages (47). Cerebral hemorrhages are also associated with increased rodent head tilts in an ischemia reperfusion injury model, independent of an infection being present (48, 49).…”

Evaluation of malaria pathology development in a group of CB6F1 mice produced in the laboratory animal facilities of INDICASAT AIP

“…Similar results were reported in assays with C57BL/6 mice, however, 24,12,25 parasitaemias higher than 80% have also been reported for this strain by the 14th day post infection. 26 As for the BALB/c mice parasitaemia, distinct results have been reported, with increases and decreases throughout the course of infection, even reporting hyperparasitaemias. 27 Figure 1 Parasitaemia of infected mice.…”

“…The results suggest that infection with Plasmodium berghei can affect many neurological functions in mice of the C57BL/6 and Cb6F1 strains. 26…”

Characterization of sulfated polysaccharide activity against virulent Plasmodium falciparum PHISTb/RLP1 protein

“…The drug activity of this compound supports its investigation as an antimalarial with further chemical modifications to suit rules of a drug compound. Carrageenan compounds antimalarial activity had previously been reported, however, the compound had to be further modified to reduce its toxicity ( Adams et al ., 2005 ; Recuenco et al ., 2014 ). The compound interacted optimumly with the refence and mutant protein through different hydrogen bonds as well as van der walls forces as shown in Figure 4 below.…”