Antimalarial properties of n-3 and n-6 polyunsaturated fatty acids: in vitro effects on Plasmodium falciparum and in vivo effects on P. berghei.

Abstract

The polyunsaturated fatty acids docosahexaenoic acid (C22.,63), eicosapentaenoic acid, arachidonic acid, and linoleic acid caused marked in vitro growth inhibition of Plasmodium falciparum, assessed by a radiometric assay. In contrast, negligible parasite killing was seen with oleic acid or docosanoic acid. Parasite killing was significantly increased when oxidized forms of polyunsaturated fatty acids were used. Antioxidants greatly reduced the fatty acid-induced killing. Mice infected with P. berghei and treated for 4 d with C22:6,,.3 showed marked reduction in parasitemia. The anemia associated with the infection was also alleviated by treatment with C22A6,,3. The data provide new information that could be explored in order to develop new strategies in malaria treatment. (J. Clin. Invest. 1992. 89:961-967.)

Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-plasmodium toxicity

“…This is in agreement with previous data reporting the involvement of the FA structure in their anti-Plasmodium activity (28). AA and DHA are the most lethal, with a 0.8-2.4 mg/ml (5.3 6 2.6 mM) and a 1.4-3.6 mg/ml (7.8 6 3.2 mM) IC 50 , respectively.…”

“…The in vitro and in vivo antimalarial effects of NEFAs have long been known (28,51,52). Our results are in accordance with the observation by Kumaratilake and coworkers (28) that the antiplasmodial activity of NEFAs is dependent on the number of double bonds of the carbon chain.…”

“…In our case, antioxidants (a-tocopherol, BHT) did not significantly alter the toxicity of the bvPLA 2 -digested lipoproteins (unpublished observations), suggesting that peroxidation is not primarily responsible for their toxicity. It must be noted that intraerythrocytic degeneration (condensation) of P. falciparum upon incubation with FAs was also observed in those studies (28,51), reinforcing the idea that NEFAs are directly responsible for the parasiticidal activity of the lipolyzed lipoproteins. Interestingly, the antimalarial activity of DHA, AA, and LA has been demonstrated in vivo: DHA and AA are capable of inhibiting the growth of Plasmodium berghei in BALB/c mice and of preventing the malaria-induced anemia (28), whereas LA provokes a substantial reduction of parasitemia in Swiss mice infected with Plasmodium vinckei petteri (51).…”

“…The lipid moiety of lipoproteins can undergo major modifications, among which is the formation of peroxides, aldehydes, oxysterols, lysoPLs, and NEFAs, resulting from intrinsic PLA 2 (PAF-acetyl hydrolase) activity in apoB-100-containing particles (46). Interestingly, it has been shown that Plasmodium is sensitive to oxidized FAs (28) and to peroxidation-intermediate molecules (47). Changes in the structure of the lipoprotein particle may also contribute to the toxicity by conferring new properties to the lipoprotein.…”

Synthesis and Biological Activity of Fatty Acid Derivatives of Quinine

“…As major components of polyunsaturated fatty acids (PUFA) in marine fish oil, docosahexaenoic acid (DHA) and icosapentaenoic acid (EPA) have a non-conjugated all cis-polyunsaturated olefinic structure and are known to exhibit a variety of biochemical, physiological functions, including enhancement of cell membrane permeability, 1) growth regulation or apoptosis-inducing capability to cancer cells, 2,3) cytotoxicity enhancement for some anti-cancer drugs against cancer cells, 4,5) and potential antimalarial activity. [6][7][8][9] If we assume that these physiological functions are mainly responsible for their characteristic olefinic structure, the same functions are also expected to play their roles even when these acids are linked to their other bioactive compounds. Here, in the present study, a series of saturated fatty acid-or PUFA-derivatives (2)-(8) of quinine ( Fig.…”