Deferiprone-Resveratrol Hybrid, an Iron-Chelating Compound, Acts as an Antimalarial and Hepatoprotective Agent in Plasmodium berghei-Infected Mice

Hataichanok Chuljerm; Supawadee Maneekesorn; Chuchard Punsawad; Voravuth Somsak; Yongmin Ma; Jetsada Ruangsuriya; Somdet Srichairatanakool; Pimpisid Koonyosying

doi:10.1155/2022/3869337

Deferiprone-Resveratrol Hybrid, an Iron-Chelating Compound, Acts as an Antimalarial and Hepatoprotective Agent in Plasmodium berghei-Infected Mice

Bioinorg Chem Appl. 2022 Nov 24:2022:3869337. doi: 10.1155/2022/3869337. eCollection 2022.

Authors

Hataichanok Chuljerm^{1

2

3}, Supawadee Maneekesorn⁴, Chuchard Punsawad⁵, Voravuth Somsak¹, Yongmin Ma⁶, Jetsada Ruangsuriya⁷, Somdet Srichairatanakool⁷, Pimpisid Koonyosying⁷

Affiliations

¹ School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand.
² School of Health Sciences Research, Research Institute for Health Sciences Chiang Mai University, Chiang Mai 50200, Thailand.
³ Environmental and Occupational Health Sciences and Non Communicable Diseases Research Group (EOHS and NCD Research Group), Research Institute for Health Sciences Chiang Mai University, Chiang Mai 50200, Thailand.
⁴ Faculty of Medical Technology, Nation University, Lampang 52000, Thailand.
⁵ School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand.
⁶ School of Pharmaceutical Sciences, Taizhou University, Zhejiang 318000, China.
⁷ Department of Biochemistry, Faculty of Medicine Chiang Mai University, Chiang Mai 50200, Thailand.

Abstract

Free heme in plasma acts as a prooxidant; thus, it is bound to hemopexin and eliminated by the liver. High iron content in the liver can support Plasmodium growth and cause oxidative liver injury. Inversely, the withholding of excessive iron can inhibit this growth and protect the liver against malaria infection. This study examined the effects of a deferiprone-resveratrol (DFP-RVT) hybrid on malaria parasites and its relevant hepatoprotective properties. Mice were infected with P. berghei, gavage DFP-RVT, deferiprone (DFP), and pyrimethamine (PYR) for 8 consecutive days. Blood and liver parameters were then evaluated. The presence of blood-stage parasites was determined using the microscopic Giemsa staining method. Subsequently, plasma liver enzymes, heme, and concentrations of thiobarbituric acid-reactive substances (TBARS) were determined. The liver tissue was examined pathologically and heme and TBARS concentrations were then quantified. The results indicate that the suppression potency against P. berghei growth occurred as follows: PYR > DFP-RVT hybrid > DFP. Importantly, DFP-RVT significantly improved RBC size, restored alanine aminotransferase and alkaline activities, and increased heme and TBARS concentrations. The compound also reduced the liver weight index, heme, and TBARS concentrations significantly when compared to mice that were untreated. Our findings support the contention that the hepatoprotective effect of DFP-RVT is associated with parasite burden, iron depletion, and lipid peroxidation in the host.