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.
Highlights
There is an urgent need to develop and test novel compounds against malaria infection
These findings differ from the report by James and Alger [2], who found that A/J Swiss mice infected with P. berghei NK65 survived for up to 28 days when pre-treated with calcium carrageenan intraperitoneally, and from the finding of Adams that λcarrageenan effectively inhibited the growth and invasion of red blood cells by P. falciparum in in vitro experiments [1]
Signs observed in the PbN mice that started to die from day 7 until day 13 p.i. included general weakness and lethargy, while signs that are related to Experimental cerebral malaria (ECM), limb paralysis, convulsions, and head tilt were not seen
Summary
There 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. 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. Carrageenan-induced inflammation in the paw of mice or rats is a classic model of oedema formation and hyperalgesia that is useful in the development of non-steroidal anti-inflammatory drugs. Among the three types of carrageenan, κ-carrageenan was found to be the most inflammatory in the paw oedema model, whereas λ-carrageenan had the highest anticoagulant activity in vitro [7]
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