Malondialdehyde and CA II autoantibody levels are elevated in children with undescended testes.

PURPOSE: In the pathogenesis of sub-fertility/infertility and testicular cancer related to undescended testes, oxidative stress, inflammation and autoimmunity are important factors. Therefore, the present study was designed to determine serum oxidative stress markers and carbonic anhydrase (CA) II autoantibodies in boys with undescended testes (UDT), and to investigate the relationship between these parameters. METHODS: Serum CA II autoantibody titers, malondialdehyde (MDA), ischemia modified albumin (IMA), protein carbonyl content and soluble CD40 ligand (sCD40L) levels were measured in 59 boys with UDT and 30 healthy subjects. RESULTS: MDA levels were significantly higher in the UDT group compared with the control group (p = 0.003). There was no significant difference between serum IMA, sCD40L or protein carbonyl levels. CA II autoantibody titers in the UDT group were significantly higher compared with those of the control group (p = 0.048). A weak positive correlation was determined between anti-CA II antibody titers and MDA and IMA levels (p = 0.041, p = 0.005, respectively). CONCLUSIONS: MDA is the most reliable and decisive biochemical marker displaying oxidative damage in undescended testes, and an autoimmune response may be triggered by oxidative stress against CA II during the UDT process.

Oxidative modification of carbonic anhydrase by peroxynitrite trigger immune response in mice and rheumatic disease patients.

BACKGROUND: Carbonic anhydrases (CA) are metalloenzymes with wide tissue distribution, involved in many important physiological processes, and in some rheumatic diseases, autoantibodies are formed against these enzymes. Recent studies have suggested that oxidative stress triggers anti-CA antibody formation. In this study, we aimed to investigate the effects of modification with oxidative/nitrosative stress end products on CA antigenicity in mice and the relationship between the modified CA autoantibodies and oxidant-antioxidant status in patients with rheumatoid arthritis (RA) and Sjögren's syndrome (SjS). METHODS: CA I and CA II isoenzymes were isolated from human erythrocytes and modified with 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and peroxynitrite (PN). Balb-c mice were immunized with these agents to determine the effects of modification on CA antigenicity. The autoantibody titers of modified CA isoenzymes were detected in patients. In addition MDA, 4-HNE, 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were measured to assess the oxidant-antioxidant status in patients. RESULTS: Modifications of carbonic anhydrase with oxidative stress end products, HNE, MDA and PN, lead to alterations in the immune response to these enzymes in mice. It was found that HNE and MDA decreased the antigenicity while PN increased. In addition, PN-modified CA autoantibody levels were found to be significantly different in both RA and SjS patients compared to their controls (p<0.05). CONCLUSIONS: PN modifications can also trigger an immune response against CA isoenzymes in mice, and PN-modified CA I and CA II autoantibody titers were found at a significantly high level in both RA and SjS patients.

Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model.

OBJECTIVES: Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. MATERIALS AND METHODS: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. RESULTS: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. CONCLUSION: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

The effect of erythrocyte membranes from diabetic and hypercholesterolemic individuals on human carbonic anhydrase II activity.

CONTEXT: Erythrocyte membranes regulate many enzyme activities, including carbonic anhydrase II (CA II). Membrane fluidity is associated with alterations in protein function and protein-protein interactions. OBJECTIVE: The purpose of this study was to show the human CA II (hCA II) activity regulation by human erythrocyte membranes from diabetic and hypercholesterolemic subjects. MATERIALS AND METHODS: Erythrocyte membranes were obtained from diabetic, hypercholesterolemic, and healthy subjects. hCA II activity was measured using the electrometric method. RESULTS: hCA II activity was increased in vitro by membranes from both diabetic and hypercholesterolemic patients, with hypercholesterolemic membranes exhibiting a greater increase. CONCLUSION: Changes in membrane composition may affect the erythrocyte membranes' capacity to increase in vitro hCA II activity.

Determination of skin wound age by using cytokines as potential markers.

Interleukin-1 beta (IL-1ß), IL-6, tumour necrosis factor-alpha (TNF-α) and epidermal growth factor (EGF) play important roles in the wound healing process. In the present study, human wound specimens (n = 50) were collected from cases of death due to injuries from firearms, penetrating trauma by sharp objects and blunt trauma with a known time of injury and death identified by forensic autopsy. Full-thickness tissue specimens were obtained from injured skin sites, and equally sized intact tissues obtained from the same person were used as controls. Protein determination was performed using ELISA according to the Bradford method for each specimen, and results were provided for individual proteins. IL-1ß levels did not reach statistical significance in any of the wound groups and were not markedly higher than those in the control group. However, IL-6 showed a biphasic pattern and reached statistical significance in the group with wounds less than 30 min old and in the group with wounds more than 18 h old. IL-6 was consistently higher in all wound groups than in the control group. TNF-α showed a statistically significant increase within the first 30 min and remained at a high level in all groups except for those with wounds 2-4 h old. On the other hand, EGF was high in all groups excluding those with wounds 2-4 h old and more than 18 h old, but statistical significance was not reached. Our results suggest that IL-6 and TNF-α in particular may be used as early-phase markers. We believe that IL-1ß and EGF should be more extensively evaluated in further studies.

Carbonic anhydrase II autoantibody and oxidative stress in rheumatoid arthritis.

OBJECTIVES: To investigate the relationship between carbonic anhydrase (CA) II autoantibody and lipid peroxidation, certain antioxidant parameters, and cytokines in rheumatoid arthritis (RA) patients. DESIGN AND METHODS: Serum levels of CA II autoantibody, cytokines (TNFα, IL-6, IFN-γ, IL-1ß) and bone markers (crosslaps, osteocalcine) and erythrocyte levels of antioxidant enzyme activities (SOD, CAT, GPx), GSH and MDA, and CA activities were measured in RA patients and healthy controls. RESULTS: The CA II autoantibody titers were significantly higher (P<0.05), and erythrocyte SOD activities were significantly lower (P<0.05) in RA patients. A significant negative correlation between CA II autoantibody titers and SOD activities in RA group was established (r=-0.430, p=0.006). The elevated cytokine levels could not be correlated with CA II autoantibody levels in RA. CONCLUSION: These results suggest that increased erythrocyte oxidative stress observed in RA may be effective in the mechanism of CA II autoantibody formation.