Cherupanakkal Cleetus, Ramachadrappa Vijayakumar, Kadhiravan Tamilarasu, Parameswaran Narayanan, Parija Subhash Chandra, Pillai Agieshkumar Balakrishna, Rajendiran Soundravally
Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605 006 India.
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Indian J Clin Biochem. 2017 Oct;32(4):437-445. doi: 10.1007/s12291-017-0633-x. Epub 2017 Jan 16.
Dengue is an arthropod-borne threat among tropical countries. Currently no effective means to treat the virus or to predict which patient will develop the severe form of the disease. Recently the relationship between oxidative/antioxidative response and dengue pathogenesis was suggested. Based on this the present study has analysed the expression of endogenous antioxidant genes: Catalase (CAT), Superoxide dismutase (MnSOD) and Glutathione peroxidase in patients with dengue compared to other febrile illness (OFI) and healthy controls. The study enrolled 88 dengue confirmed patients comprising 56 were patients with non-severe dengue, and 32 were severe dengue cases, 31 were patients with OFI, and 63 healthy controls were also involved. Peripheral blood mononuclear cells isolated from patients and controls during the day of admission and from the available cases on the day of defervescence were used to estimate the transcript levels by quantitative PCR. The expression levels of all the three genes were found to be down-regulated throughout the course of dengue infection ( < 0.05) and OFI cases compared to healthy controls. Within dengue group, no significant difference was observed in any of the parameters between severe and non-severe cases. Interestingly, a significant down-regulation of MnSOD expression was recorded in secondary dengue infection compared to primary during admission ( < 0.05). It was found that all the down-regulated study genes have positively correlated in all dengue cases during the day of admission ( < 0.01). But during defervescence, the same was found only between CAT and MnSOD. Down-regulated endogenous antioxidant enzymes during dengue infection could be the possible rationale of oxidative stress reported in dengue disease earlier. The present study markers could not distinguish dengue from OFI cases and severe from non-severe dengue cases. Mechanism of down-regulation has to be explored further which will pave the way for the therapeutic target in dengue disease.
登革热是热带国家中由节肢动物传播的一种威胁。目前尚无有效的方法来治疗该病毒或预测哪些患者会发展为重症疾病形式。最近有人提出氧化/抗氧化反应与登革热发病机制之间的关系。基于此，本研究分析了内源性抗氧化基因：过氧化氢酶（CAT）、超氧化物歧化酶（MnSOD）和谷胱甘肽过氧化物酶在登革热患者中的表达，并与其他发热性疾病（OFI）患者和健康对照进行了比较。该研究纳入了88例确诊为登革热的患者，其中56例为非重症登革热患者，32例为重症登革热病例，31例为OFI患者，还纳入了63名健康对照。在入院当天从患者和对照中分离出外周血单核细胞，并从退热当天的现有病例中分离出外周血单核细胞，用于通过定量PCR估计转录水平。与健康对照相比，发现这三个基因的表达水平在登革热感染全过程（P<0.05）以及OFI病例中均下调。在登革热组内，重症和非重症病例之间在任何参数上均未观察到显著差异。有趣的是，与入院时的初次登革热感染相比，二次登革热感染时MnSOD表达有显著下调（P<0.05）。发现在入院当天所有登革热病例中，所有下调的研究基因均呈正相关（P<0.01）。但在退热期，仅在CAT和MnSOD之间发现同样的情况。登革热感染期间内源性抗氧化酶下调可能是早期登革热疾病中报道的氧化应激的可能原因。本研究中的标志物无法区分登革热与OFI病例，也无法区分重症与非重症登革热病例。下调机制有待进一步探索，这将为登革热疾病的治疗靶点铺平道路。
