Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model.
Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model.
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DOI：
10.1186/1475-2875-11-13
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发表时间：
2012-01-10
期刊：
影响因子：
3
通讯作者：
Pradines B
中科院分区：
文献类型：
--
作者：
Souraud JB;Briolant S;Dormoi J;Mosnier J;Savini H;Baret E;Amalvict R;Soulard R;Rogier C;Pradines B
恶性疟原虫感染的主要并发症之一是脑型疟疾（CM），每年在全球造成一百万人死亡，导致长期神经系统后遗症，而治疗仅部分有效。他汀类药物被认为具有免疫调节作用、减轻脓毒症并具有神经保护作用。阿托伐他汀 (AVA) 在体外显示出抗疟疾活性，并提高了甲氟喹 (MQ) 和奎宁的活性。在实验性伯氏疟原虫 ANKA 啮齿动物 CM 寄生虫模型中评估了 40 mg/kg 腹腔内 AVA 单独或与 MQ 联合使用的效率，并根据不同的治疗方案进行。通过TUNEL染色评估脑组织病理学变化和神经元凋亡来评估对实验CM的影响。治疗方案中单独使用 AVA 对生存没有影响，但采用 AVA 与 MQ 相关的预防方案，而不是单独使用 MQ，导致小鼠死亡显着延迟，并对 CM 症状的发作和寄生虫血症水平产生影响。组织病理学结果显示脑损伤与 CM 发病之间存在相关性。 AVA + MQ 组合中未显示 AVA 的神经元抗凋亡作用。 AVA 和 MQ 疗法的结合导致小鼠死亡率显着延迟。小鼠联合用药时，脑型疟的发病率、发生时间以及寄生虫血症水平存在差异。当与 MQ 联合使用时，AVA 对伯氏疟原虫 ANKA 感染小鼠的体内生长抑制和临床结果具有相关作用。
One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine. The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining. AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown. The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.
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影响因子：
5
作者：
Grip, O;Janciauskiene, S;Lindgren, S
通讯作者：
Lindgren, S
影响因子：
4.4
作者：
Hansen, Diana S.;Bernard, Nicholas J.;Schofield, Louis
通讯作者：
Schofield, Louis
影响因子：
5
作者：
Lackner, P;Beer, R;Schmutzhard, E
通讯作者：
Schmutzhard, E
影响因子：
11
作者：
Huang, KC;Chen, CW;Lin, WW
通讯作者：
Lin, WW
影响因子：
8.3
作者：
Moonis, M;Kane, K;Fisher, M
通讯作者：
Fisher, M