Alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice

• Main Authors: Takeya Motohiro, Yokoyama Naoaki, Fukumoto Shinya, Shichiri Mototada, Ishibashi Kana, Chiba Mayumi, Ichikawa Chie, Ueta Yoshiko Y, Herbas Maria S, Xuan Xuenan, Arai Hiroyuki, Suzuki Hiroshi
• Format: Article
• Language: English
• Published: BMC 2010-04-01
• Series: Malaria Journal
• Online Access: http://www.malariajournal.com/content/9/1/101

<p>Abstract</p> <p>Background</p> <p>Various factors impact the severity of malaria, including the nutritional status of the host. Vitamin E, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect <it>Plasmodium </it>development. However, mechanisms of this <it>Plasmodium </it>inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear.</p> <p>Methods</p> <p>α-TTP knockout mice were infected with <it>Plasmodium berghei </it>NK65 or <it>Plasmodium yoelii </it>XL-17, parasitaemia, survival rate were monitored. In one part of the experiments mice were fed with a supplemented diet of vitamin E and then infected. In addition, parasite DNA damage was monitored by means of comet assay and 8-OHdG test. Moreover, infected mice were treated with chloroquine and parasitaemia and survival rate were monitored.</p> <p>Results</p> <p>Inhibition of α-tocopherol transfer protein (α-TTP), a determinant of vitamin E concentration in circulation, confers resistance to malarial infection as a result of oxidative damage to the parasites. Furthermore, in combination with the anti-malarial drug chloroquine results were even more dramatic.</p> <p>Conclusion</p> <p>Considering that these knockout mice lack observable negative impacts typical of vitamin E deficiency, these results suggest that inhibition of α-TTP activity in the liver may be a useful strategy in the prevention and treatment of malaria infection. Moreover, a combined strategy of α-TTP inhibition and chloroquine treatment might be effective against drug resistant parasites.</p>