Crocetin Improves Dengue Virus-Induced Liver Injury

Gopinathan Pillai Sreekanth,Thawornchai Limjindaporn,Pa-Thai Yenchitsomanus,Aporn Chuncharunee

doi:10.3390/v12080825

Gopinathan Pillai Sreekanth, Thawornchai Limjindaporn + Show 2 more

Open Access

https://doi.org/10.3390/v12080825

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Journal: Viruses	Publication Date: Jul 30, 2020
Citations: 15	License type: CC BY 4.0

Affiliation: Siriraj Hospital, Mahidol University

Abstract

Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.

Highlights

Dengue virus (DENV) belongs to the Flaviviridae family, and it comprises four antigenically distinct serotypes
7A,B) andmice; p38 (Figure significantly elevated in the liver protein were treated with crocetin (Figure samples of DENV-infected mice; these phosphorylation events were observed to be reduced upon crocetin treatment (Figure 7A–D). These results suggest the efficacy of crocetin for modulating
We identified that crocetin treatment did not have any direct impact on DENV production in the liver of DENV-infected mice, which suggests the improvements in the liver injury were possibly attained via modulating these host responses

Summary

Introduction

Dengue virus (DENV) belongs to the Flaviviridae family, and it comprises four antigenically distinct serotypes (serotypes 1–4). The manifestations of DENV infection include symptoms that range from mild dengue fever (DF) to the more severe forms that include dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [2]. Liver injury is very frequently identified in severe dengue infection [3], and it has been found to be correlated with the clinical pathology [4,5]. An example of this relationship was the observed elevation of aminotransferases. The World Health Organization (WHO) has included liver injury as one of the major disease criteria for severe forms of DENV infection [7].

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