Anti-Malarial and Anti-Lipid Peroxidation Activities of Deferiprone-Resveratrol Hybrid in Plasmodium berghei-Infected Mice

SIMPLE SUMMARY: Malaria remains a public health problem in tropical and subtropical countries. The emergence of malaria parasite resistance to antimalarial drugs has been recently considered a serious issue. Alternative compounds have become an important therapeutic strategy to achieve malaria treatment. Iron chelators are widely used for the treatment of iron overload patients. The iron chelators also reveal an inhibitory effect on malaria parasite growth by depriving the parasite intracellular iron. This study presented the potential of the novel hybrid iron chelator, deferiprone-resveratrol hybrid on the inhibition of malaria parasite growth, the improvement of hematological parameters and the alleviatation of oxidative tissue damage in malaria-infected mice. Deferiprone-resveratrol hybrid would be used as a therapeutic/preventive compound to increase the efficacy of treatment and eliminate an antimalarial drug resistance. ABSTRACT: Iron is essential for all organisms including fast-dividing malarial parasites. Inversely, iron chelators can inhibit parasite growth through the inhibition of DNA synthesis and can ameliorate oxidative cell damage. Deferiprone (DFP)-resveratrol (RVT) hybrid (DFP-RVT) is a lipophilic anti-oxidative, iron-chelating agent that has displayed potent neuroprotective and anti-plasmodium activities in vitro. The goal of this work was to investigate the inhibitory effects of DFP-RVT on parasite growth and oxidative stress levels during malaria infections. Mice were intraperitoneally infected with P. berghei and orally administered with DFP, DFP-RVT and pyrimethamine for 4 d. The percentage of parasitemia was determined using Giemsa’s staining/microscopic examination. Amounts of the lipid-peroxidation product, thiobarbituric acid-reactive substance (TBARS), were determined in both plasma and liver tissue. In our findings, DFP-RVT exhibited a greater potent inhibitory effect and revealed an improvement in anemia and liver damage in infected mice than DFP. To this point, the anti-malarial activity was found to be associated with anti-RBC hemolysis and the liver weight index. In addition, plasma and liver TBARS levels in the DFP-RVT-treated mice were lower than those in DFP-treated mice. Thus, DFP-RVT could exert anti-plasmodium, anti-hemolysis and anti-lipid peroxidation activities to a better degree than DFP in P. berghei-infected mice.