Instituto de Ciências Biológicas, Laboratório de Neurofarmacologia Experimental, Universidade Federal do Pará, Belém, Pará, Brazil.
Núcleo de Medicina Tropical, Laboratório de Neurologia Tropical, Universidade Federal do Pará, Belém, Pará, Brazil.
Biomed Res Int. 2021 Sep 4;2021:9694508. doi: 10.1155/2021/9694508. eCollection 2021.
Malaria is a life-threatening disease caused by and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of -infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition.
疟疾是一种由 引起的危及生命的疾病，是世界上主要的公共卫生问题之一。在与该疾病相关的改变中，我们强调了由氧化应激产生的肝损伤。研究表明， 感染引起的肝损伤与肝细胞抗氧化系统失衡有关，尽管对于抗氧化分子如谷胱甘肽和维生素 C 在疾病进展和肝损伤中的作用知之甚少。为了评估疾病的并发症，由于人类和小鼠感染的物种之间存在相似性，鼠模型成为一种有价值的工具。在此，本研究旨在评估抗氧化剂谷胱甘肽和维生素 C 对小鼠疟疾的进展以及 ANKA 感染引起的肝损伤的影响。小鼠接种感染的红细胞，并分别用谷胱甘肽和维生素 C 处理，两者均在连续 7 天内以 8mg/kg 的剂量处理。我们的数据表明，在 感染期间，用谷胱甘肽处理可显著降低感染小鼠的存活率，加速疾病的严重程度。然而，用维生素 C 处理可改善临床结果并延长感染动物的存活曲线。我们还表明，谷胱甘肽可提高 -感染动物的疟原虫血症率，尽管用维生素 C 处理可诱导疟原虫血症率显著降低。此外，组织学分析和酶生化测量表明，用谷胱甘肽处理可加重肝损伤，而用维生素 C 处理可减轻感染引起的肝损伤。总之，本研究提供了证据表明抗氧化分子可不同地调节疟疾疾病的结局；谷胱甘肽加重了疾病结局和肝损伤，而维生素 C 的治疗可保护肝脏免受损伤和病情恶化。
