Search

Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([ 68 Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [ 68 Ga]Ga-SKN by Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , and S. epidermidis , but no uptake by Candida glabrata , C. albicans , or Aspergillus fumigatus , demonstrated its specificity to bacterial species. Whole-body [ 68 Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [ 68 Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.

Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone-resveratrol hybrid (DFP-RVT) is a synthetic iron chelator possessing anti-β-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP-RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells. In the findings, DFP-RVT dose dependently bound Fe(II) and Fe(III) and exerted stronger ABTS • - and DPPH • -scavenging (IC 50 = 8.0 and 164 μM, respectively) and anti-RBC hemolytic activities (IC 50 = 640 μM) than DFP but weaker than RVT ( p < 0.01). DFP-RVT was neither toxic to Huh7 cells nor PBMCs. In addition, DFP-RVT diminished the level of redox-active iron ( p < 0.01) and decreased the non-heme iron content ( p < 0.01) in iron-loaded Huh7 cells effectively when compared without treatment in the order of DFP-RVT > RVT ∼ DFP treatments (50 µM each). Moreover, the compound decreased levels of hepatic ROS in a dose-dependent manner and the level of malondialdehyde, which was stronger than DFP but weaker than RVT. Furthermore, DFP-RVT restored the decrease in the GSH content and GPX and SOD activities ( p < 0.01) in iron-loaded Huh7 cells in the dose-dependent manner, consistently in the order of RVT > DFP-RVT > DFP. Thus, the DFP-RVT hybrid possesses potent iron chelation, antioxidation, anti-lipid peroxidation, and antioxidant defense against oxidative liver damage under iron overload., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Koonyosying, Korsieporn, Paradee, Hutachok, Xu, Ma, Chuljerm and Srichairatanakool.)

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hataichanok Chuljerm et al.)