Abstract
Malaria is a life-threatening disease caused by Plasmodium 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 Plasmodium 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 Plasmodium berghei 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 Plasmodium 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 Plasmodium-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.
Highlights
Malaria represents one of the major and oldest public health problems in developing countries [1, 2]
Our data showed that during Plasmodium berghei ANKA (PbA) infection, nontreated animals were able to survive until 29 days postinfection; the treatment with 8 mg/kg GSH promoted a significant decrease in the survival of PbA-infected mice, with animals dying between days 17 and 19 postinfection (d.p.i)
We observed that 100% of PbAinfected animals treated with GSH died in the 23rd d.p.i. while the PbA-infected group survived until the 29th d.p.i. (Figure 1(a))
Summary
Malaria represents one of the major and oldest public health problems in developing countries [1, 2]. As widely described in literature, malaria disease is caused by infection with species of Plasmodium spp. This parasite presents a complex life cycle involving different stages of development in both mosquito and human hosts [8, 9]. Ookinetes and sporozoites are the life forms of Plasmodium found in a definitive mosquito host, and the sporozoites are responsible for infecting hepatocytes in the liver of a vertebrate host. The liver is considered a Plasmodium “depository” being an essential organ to the development of malaria disease. Kupffer cell hyperplasia, hemozoin deposition, and monocyte infiltration are frequent histological alterations described in the malaria hepatopathy [15, 16]
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