Acta Tropica 106 (2008) 156–161 Contents lists available at ScienceDirect Acta Tropica journal homepage: www.elsevier.com/locate/actatropica Oxidative stress induced changes in plasma protein can be a predictor of imminent severe dengue infection R. Soundravally a,∗ , P. Sankar b , S.L. Hoti a , N. Selvaraj b , Z. Bobby b , M.G. Sridhar b a Department of Molecular Biology and Bioinformatics, Vector Control Research Centre (VCRC), Pondicherry, India b Deparment of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India article info Article history: Received 18 November 2007 Received in revised form 3 March 2008 Accepted 4 March 2008 Available online 13 March 2008 Keywords: Oxidative stress Severe dengue infection Protein carbonylation Protein-bound sulphydryl groups abstract Objectives: Oxidative stress in dengue viral infection has been suggested and severity of it was found to be associated with progress of illness. Hence assessing oxidative stress mediated changes in plasma proteins can be an early biomarker for prediction of severe dengue infection. Design and methods: Thirty two dengue hemorrhagic fever (DHF), 21 dengue shock syndrome (DSS), 27 dengue fever (DF) and 63 age and sex matched controls, were included in this study. Blood samples were collected on the 3rd day of fever. Protein carbonylation (PCOs) and protein-bound sulphydryl (PBSH) group levels were determined by spectrophotometric method and analyzed as predictor of dengue hemorrhagic fever and dengue shock syndrome. Results: About 80–84% of cases presented with no signs of DHF/DSS at the time of sampling. Dengue infected individuals had significantly elevated PCOs and low PBSH group levels than the controls. Using one-way ANOVA we found a significant difference with high PCOs and low PBSH group levels between DHF and DSS when compared with DF (P <0.001). However, no difference was observed in PBSH group levels between DHF and DSS. A significant difference in PCOs to PBSH ratio was observed among DF, DHF and DSS (P < 0.001). Linear regression analysis revealed that duration of hospitalization is dependent on PCOs and PBSH group levels. Receiver operator curve (ROC) analysis indicated that 5.22nmol/mg protein PCOs; 1.08 PCOs to PBSH group levels ratio were optimal cutoff value for predicting DHF with sensitivity and specificity of 87.5% and 74.1%; 96.9% and 81.5%, respectively. For DSS prediction, 6.13 nmol/mg protein PCOs; 1.16 PCOs to PBSH group levels ratio were found as effective cutoff with sensitivity and specificity of 81% and 71.9%; 95.2% and 56.2%, respectively. Conclusion: Oxidative stress has been observed to develop since early days of onset of dengue infection. Plasma PCOs, PCOs to PBSH group ratio were found to very well predict DHF/DSS. © 2008 Published by Elsevier B.V. 1. Introduction Dengue fever (DF) is emerging to be a cause of concern in the tropics and growing threat in industrialized nations. The patho- genesis of dengue fever is poorly understood. In secondary dengue hemorrhagic fever (DHF) cases, higher viremia is observed and antibody dependent enhancement of viral entry into phagocytic cells has been hypothesized as the causative factor (Halstead, 1988; Kurane and Takasaki, 2001). However, the mechanism by which high viremic status induces DHF is not clear. Aberrant cytokine secretion with polarity towards Th1 response is also sug- gested as another risk factor for DHF/dengue shock syndrome (DSS) (Chatuverdi et al., 2000). In dengue viral infection, prolonged acti- vation of T cells and their apoptosis has been proposed as a cause ∗ Corresponding author. Tel.: +91 9942142567; fax: +91 413 2272041. E-mail address: soundy27@yahoo.co.in (R. Soundravally). for delayed viral clearance (Mongkolsapaya et al., 2003). While the pathogenesis of dengue fever is not well understood, oxidative stress appears to play an important role (Gil et al., 2004). After viral entry, immune system gets activated, which steers phagocytic and other cells to produce reactive oxygen species (ROS) to destroy the invading organism (Peterhans et al., 1987). There is now much evidence that oxidants play a complex role in viral diseases, starting from influences on host cell metabolism to less desired toxic effects on host tissue (Yoshikawa, 2002; Sahnoun et al., 1997; Schwarz, 1996). Oxidants are highly unstable and react with nucleic acid, lipids, proteins, carbohydrate or any other molecule causing a cascade of chain reactions resulting in cellular damage. This process might cause loss of fluidity and production of protein and lipid peroxides which leads to cell wall destruction. Evidence for oxidative injury comes predominately from mea- surement of biochemical markers of lipid peroxidation and protein oxidation. Malondialdehyde (MDA) and protein carbonyls (PCOs) are by-products of oxidation of lipids and proteins, respectively 0001-706X/$ – see front matter © 2008 Published by Elsevier B.V. doi:10.1016/j.actatropica.2008.03.001