8-hydroxy-2--deoxyguanosine and Edema

KIOM-79 is a mixture of 80% ethanol extracts of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix. The preventive effect of KIOM-79 on the development of diabetic keratopathy has been investigated.. Seven-week-old male Zucker diabetic fatty (ZDF) rats were treated with KIOM-79 (50 mg/kg body weight) once a day orally for 13 weeks. The thickness of the cornea was measured and the extent of corneal cell death was detected by a terminal deoxynucleotidyl transferase dUTP nick-end labelling assay. The expression of advanced glycation end products (AGEs), 8-hydroxydeoxyguanosine, nuclear factor-kappaB (NF-κB), Bax and Bcl-2 were evaluated in corneal tissues.. The administration of KIOM-79 prevented corneal oedema and apoptotic cell death of corneal cells. The accumulation of AGE in corneal tissues was reduced in ZDF rats treated with KIOM-79. Moreover, KIOM-79 attenuated oxidative DNA damage, NF-κB activation and Bax overexpression in the cornea.. The results suggested that KIOM-79 exhibited corneal protective properties by not only reducing oxidative stress but inhibiting the AGEs/NF-κB downstream signal pathway during the development of diabetic keratopathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Blood Glucose; Cell Death; Cornea; Deoxyguanosine; Diabetes Complications; Edema; Glycation End Products, Advanced; Male; NF-kappa B; Oxidative Stress; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Zucker; Signal Transduction

Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Behavior, Animal; Brain; Deoxyguanosine; Dietary Fats; Docosahexaenoic Acids; Edema; Eicosapentaenoic Acid; Glutathione; Hemorrhage; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stroke; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Immune arthritis in rat ankle joints was induced by intra-articular injection of streptococcal cell was extract (SCW), followed 21 days later by i.v. injection of SCW. This results in a monoarticular arthritis characterized by an influx of neutrophils and mononuclear cells, a 35-fold increase in urinary excretion of 8-hydroxy-deoxyguanosine (8-OH-dGUA; an index of free radical production), ankle edema, and joint damage/destruction. Neutrophil depletion substantially reduced the intensity of ankle edema. Ab-induced blockade of P-selectin or ICAM-1 also reduced the intensity of ankle edema and the influx of neutrophils. Blockade of TNF-alpha or IL-1 resulted in nearly complete and persistent reduction in ankle edema and profound reductions in the accumulation of neutrophils and mononuclear cells in affected joints. Finally, blocking of macrophage-inflammatory protein-2 reduced ankle edema and neutrophil accumulation during the first 2 days after i.v. challenge with SCW. These data indicate that SCW-induced arthritis is neutrophil dependent and that the recruitment of neutrophils and subsequent joint edema requires ICAM-1, P-selectin, and macrophage-inflammatory protein-2, as well as TNF-alpha and IL-1.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Arthritis; Chemokine CXCL2; Chemotactic Factors; Deoxyguanosine; Disease Models, Animal; Edema; Female; Injections, Intravenous; Intercellular Adhesion Molecule-1; Interleukin-1; Monokines; Neutropenia; Neutrophils; P-Selectin; Peptidoglycan; Rats; Rats, Inbred Lew; Time Factors; Tumor Necrosis Factor-alpha