Differential Effect of Antioxidants Glutathione and Vitamin C on the Hepatic Injuries Induced by Plasmodium berghei ANKA Infection

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.

Effects of vitamin C supplementation on Chinese sausage-induced liver damage in rats

“…In this study, MDA was elevated in rats after intake of the sausage, which can be prevented by VC supplementation; in the meantime, the activities of serum reactive oxygen species (ROS) scavengers, that is, T-SOD and GSH-PX, were enhanced while the serum MDA was lowered, by VC supplementation. As previously reported, elevation in ROS scavengers by VC supplementation contributes significantly to alleviation of lipid peroxidation (Esmaeilizadeh et al, 2020;Kauffmann et al, 2021), which could be initiated by NDMA, a potent hepatotoxicant contained in Chinese sausages.…”

Rutin ameliorates malaria pathogenesis by modulating inflammatory mechanism: an in vitro and in vivo study

“…Thus, modulation of the host in ammatory response exerted by the malaria parasite could be a considerable therapeutic approach against malaria pathogenesis such as the signalling kinases activated in the host in response to the malaria infection manifested a promising target for the antimalarial interference (Adderley et al 2020). Similarly, antioxidant molecules such as vitamin C renders its protection against the outcome of malaria pathology by regulating in ammatory response (Kauffmann et al 2021). The expansion of resistance developed by P. falciparum to the existing antimalarials has intensi ed the quest for drugs with a new mechanism of action (Rout and Mahapatra 2019).…”