Expression of 4-Hydroxynonenal (4-HNE) and Heme Oxygenase-1 (HO-1) in the Kidneys of Plasmodium berghei-Infected Mice

Acute kidney injury (AKI) is one of the most serious complications of severe Plasmodium falciparum malaria, but the exact pathogenic mechanisms of AKI in P. falciparum infection have not been clearly elucidated. We hypothesized that oxidative stress is a potential mediator of acute tubular necrosis in P. falciparum-infected kidneys. Therefore, this study aimed to investigate the histopathological changes and markers of oxidative stress in kidney tissues from mice with experimental malaria. DBA/2 mice were divided into two groups: the mice in the malaria-infected group (n = 10) were intraperitoneally injected with 1 × 106P. berghei ANKA-infected red blood cells, and the mice in the control group (n = 10) were intraperitoneally injected with a single dose of 0.85% normal saline. Kidney sections were collected and used for histopathological examination and the investigation of 4-hydroxynonenal (4-HNE) and heme oxygenase-1 (HO-1) expression through immunohistochemistry staining. The histopathology study revealed that the P. berghei-infected kidneys exhibited a greater area of tubular necrosis than those of the control group (p<0.05). The positive staining scores for 4-HNE and HO-1 expression in tubular epithelial cells of the P. berghei-infected group were significantly higher than those found for the control group (p<0.05). In addition, significant positive correlations were found between the tubular necrosis score and the positive staining scores for 4-HNE and HO-1 in the kidneys from the P. berghei-infected group. In conclusion, this finding demonstrates that increased expression of 4-HNE and HO-1 might be involved in the pathogenesis of acute tubular damage in the kidneys during malaria infection. Our results provide new insights into the pathogenesis of malaria-associated AKI and might provide guidelines for the future development of a therapeutic intervention for malaria

Trogocytosis with monocytes associated with increased α2,3 sialic acid expression on B cells during H5N1 influenza virus infection.

The immunopathogenesis of H5N1 virus has been studied intensively since it caused cross-species infection and induced high mortality to human. We previously observed the interaction between monocytes and B cells, which increased the susceptibility of B cell to H5N1 virus infection after a co-culture. Levels of α2,3 sialic acid (avian flu receptor) were also significantly increased on B cell surface in this co-culture model with unclear explanation. In this study, we aimed to determine the possible mechanism that responded for this increase in α2,3 sialic acid on B cells. Acquisition of α2,3 SA by B cells via cell contact-dependent trogocytosis was proposed. Results showed that the lack of α2,3 SA was detected on B cell surface, and B cells acquired membrane-bound α2,3 SA molecules from monocytes in H5N1-infected co-cultures. Occurrence of membrane exchange mainly relied on H5N1 infection and cell-cell contact as opposed to a mock infection and transwell. The increase in α2,3 SA on B cell surface mediated by trogocytosis was associated with the enhanced susceptibility to H5N1 infection. These observations thus provide the evidence that H5N1 influenza virus may utilize trogocytosis to expand its cell tropism and spread to immune cells despite the lack of avian flu receptor

Preclinical evaluation of antimalarial activity of CPF-1 formulation as an alternative choice for the treatment of malaria

Abstract Background Kheaw Hom remedy is a traditional Thai medicine used to treat fever. Some plants used in the Kheaw Hom remedy show promising in vitro antimalarial activity. This study prepared novel formulations of plants from the Kheaw Hom remedy and evaluated their antimalarial and toxicological activities. Methods Seven new formulations were prepared by combining at least three herbs of six selected plants from the Kheaw Hom remedy, namely Mammea siamensis Kosterm., Mesua ferrea L., Dracaena loureiroi Gagnep., Pogostemon cablin (Blanco) Benth., Kaempferia galanga L, and Eupatorium stoechadosmum Hance. In vitro antimalarial activities of each formulation’s aqueous and ethanolic extracts were evaluated using the parasite lactate dehydrogenase (pLDH) assay. Cytotoxicity in Vero and HepG2 cells was assessed using the MTT assay. An extract with good antimalarial potency and selectivity index (SI) was selected for in vivo antimalarial activity using Peter’s 4-day suppressive test and acute oral toxicity test in mice. In addition, bioactive compounds were identified using Gas chromatography-mass spectrometry (GC-MS) analysis. Results Among the seven new formulations, ethanolic extracts of CPF-1 (Formulation 1) showed the highest activity with an IC50 value of 1.32 ± 0.66 µg/ml, followed by ethanolic extracts of Formulation 4 and Formulation 6 with an IC50 value of 1.52 ± 0.28 µg/ml and 2.48 ± 0.34 µg/ml, respectively. The highest SI values were obtained for the ethanolic extract of CPF-1 that was selected to confirm its in vivo antimalarial activity and toxicity. The results demonstrated a significant dose-dependent reduction in parasitemia. Maximum suppressive effect of the extract (72.01%) was observed at the highest dose administered (600 mg/kg). No significant toxicity was observed after the administration of 2000 mg/kg. Using GC-MS analysis, the most abundant compound in the ethanolic extract of CPF-1 was ethyl p-methoxycinnamate (14.32%), followed by 2-propenoic acid, 3-phenyl-, ethyl ester, (E)- (2.50%), and pentadecane (1.85%). Conclusion The ethanolic extract of CPF-1 showed promising in vitro and in vivo antimalarial efficacy, with no toxic effects at a dose of 2000 mg/kg, suggesting that the ethanolic extract of CPF-1 may serves as a new herbal formulation for the treatment of malaria. Additional research is required for safety and clinical pharmacology studies