Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus

Abstract

Summary. -Influenza virus is well known for pandemics and epidemics with high morbidity. Many studies have been focused to this problematics, however, oxidative damage to DNA, lipids, and proteins and the expression of cytokines, antioxidant enzymes and heat-shock proteins (HSPs) in H1N1 virus-infected patients has not been investigated yet. Therefore we aimed this study at these issues. We found out that patients infected with the 2011 H1N1 virus as compared to control subjects exhibited an increased oxidative damage to DNA, lipids and proteins as assayed by levels of 8-hydroxydeoxyguanosine (8-OhdG) and malondialdehyde (MDA) and carbonyl content in plasma and urine. Moreover, the levels of antioxidant enzymes SOD and catalase, cytokines Il-6, 1L-10 and TNF-α and HSPs 90 and 27 were also significantly higher in the H1N1-infected patients. Our results suggest that the influenza H1N1 virus is a strong inducer of (i) oxidative damage to DNA, lipids, and proteins, (ii) antioxidant enzymes, (iii) cytokines and (iv) HSPs.Keywords: influenza H1N1 virus; patients; oxidative damage; antioxidant enzymes; cytokines; heat-shock proteins * Corresponding authors. E-mail: dsul@korea.ac.kr, litjacob@chol. com; phone: +82-2-920-6614. # These authors contributed equally to this work. Abbreviations: 8-OhdG = 8-hydroxydeoxyguanosine; SOD = superoxide dismutase; IL = interleukin; TNF-α = tumor necrosis factor alpha; MDA = malondialdehyde; Prx = peroxiredoxin; HSPs = heat shock proteins; ROS = reactive oxygen species

Redox Biology of Respiratory Viral Infections

“…that are oxidized by ROS into quantifiable fluorescent products or via quantification of cellular oxidation products. In patients that are infected with IV marked increases in DNA (8-hydroxydeoxyguanosine), lipid (malondialdehyde, F2-isoprostane, 7-ketocholesterol, and 7β-hydroxycholesterol), and protein (carbonyl content) oxidation products in blood plasma and urine were reported [ 23 , 24 , 25 ]. Elevated levels of sterol oxidation products were detected not only during the infection but also three months after IV clearance [ 24 ].…”

Redox control in the pathophysiology of influenza virus infection

“…Malondialdehyde, F2-isoprostane, 7-ketocholesterol, and 7β-hydroxycholesterol have been identified as lipid alterations that are induced by IV-mediated ROS [24,42]. IV infection induces oxidation, which is accompanied by an increase in the levels of lipid peroxidation in the presence of vitamin E, conjugated dienes, and total malondialdehyde [134].…”

“…In humans, IAV infection increases the levels of metabolites such as 8-hydroxydeoxyguanosine, malondialdehyde, 2-isoprostane, 7-ketocholesterol, 7-beta-hydroxycholesterol, and carbonyl compounds in the plasma and urine. The levels of antioxidant enzymes, such as SOD and catalase; cytokines, such as IL-6, 1L-10, and TNF-α; and HSPs, such as HSP90 and HSP27 were also increased in H1N1-infected patients [ 24 , 42 ]. Increased ROS, nitric oxide synthase 2 (iNOS2), and nitrotyrosine levels have been detected in patients and in a mouse model [ 43 ].…”

“…AhR activation during IV infection disrupts host immunity and causes increased lung inflammation and mortality in mice [ 42 , 64 , 165 , 172 ]. The suppression of AhR activity is assumed to attenuate IV-induced lung damage.…”

Metabolic host response and therapeutic approaches to influenza infection

“…On the other hand, PB1-F2 decreases superoxide anion dismutase 1 (SOD1) expression and consequently disrupts the ROS scavenging process [11]. In people with influenza infection, increased levels of DNA, lipid, and protein oxidation products are found in plasma and urine [12][13][14]. Also, increased levels of ROS and inducible nitric oxide synthase (iNOS) have been observed as markers of oxidative stress in the lungs of people who died due to pandemic influenza infection [15].…”