8-hydroxy-2--deoxyguanosine and Sjogren-s-Syndrome

To demonstrate the existence of oxidative stress and the role of the antioxidant thioredoxin (TRX) in Sjögren's syndrome (SS).. Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-gamma (IFN-gamma) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-gamma and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining.. Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-gamma-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX.. Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aldehydes; Antioxidants; Apoptosis; Biomarkers; Cysteine Proteinase Inhibitors; Deoxyguanosine; Female; Humans; Hydrogen Peroxide; Interferon-gamma; Interleukin-6; Middle Aged; Oxidants; Oxidative Stress; Saliva; Salivary Glands; Sjogren's Syndrome; Thioredoxins; Tyrosine

To determine the involvement of oxidative stress in the salivary gland of patients with Sjogren's syndrome (SS).. Oxidative damage to the gland was measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine (HEL) using the SS saliva. In addition, lactate dehydrogenase (LDH) and mitochondrial glutamic-oxaloacetic transaminase (m-GOT), both general markers for cell damage, were also analyzed.. Increased levels of 8-OHdG and HEL were found in the saliva of SS patients, but not in that of patients with other salivary gland dysfunction or of healthy individuals. Levels of LDH and m-GOT were significantly correlated with 8-OHdG and HEL levels, respectively. Furthermore, the increased levels of 8-OHdG and HEL were also correlated in the SS saliva.. These findings suggested the involvement of oxidative stress in glandular tissue destruction in SS. It was indicated that the detection of 8-OHdG and HEL in the saliva may become a useful tool for the diagnosis of SS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Aspartate Aminotransferases; Deoxyguanosine; Female; Humans; L-Lactate Dehydrogenase; Middle Aged; Mitochondria; Oxidative Stress; Saliva; Salivary Glands; Sjogren's Syndrome