8-hydroxyguanine and Reperfusion-Injury

To investigate the effectiveness of controlled reperfusion (CR) on ovarian tissue malondialdehyde, total glutathione and 8-hydroxyguanine levels and infertility rates in a rat model of induced ischemia-reperfusion (I/R) injury with unilateral oophorectomy.. A total of 135 adult female albino Wistar rats were divided into 9 groups (n = 15 for each group): unilateral ovariectomy + ovarian I/R (OIR), unilateral ovariectomy alone (OEG), a sham operation group (SG), and unilateral ovariectomy + CR performed at different intervals (the clips were released 10 times for 10, 8, 6, 4, 2 or 1 s and closed again 10 times for 10, 8, 6, 4, 2 or 1 s; OCR-1-6, respectively). Five rats from each group were sacrificed, and their ovaries were removed.. Higher ovarian tissue malondialdehyde and 8-hydroxyguanine levels and lower ovarian tissue total glutathione levels were found in the OIR group compared with the SG, OEG and OCR-4-6 groups. The number of rats giving birth during the study period was found to be similar among the SG (n = 8), OEG (n = 8) and OCR-6 (n = 7) groups.. These results suggest that sterility and ovarian oxidative stress caused by I/R injury decreases in parallel to the shortening of CR duration.

Topics: Animals; Female; Glutathione; Guanine; Infertility; Ischemic Preconditioning; Malondialdehyde; Ovariectomy; Ovary; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury

Reperfusion has always been "the emergency intervention" to ischemic tissue. For a given period of time, tissue injury due to ischemia and reperfusion is more serious than injury due to ischemia only. Groups were as: Group 1: 25 µg/kg dexmedetomidine + ischemia/reperfusion group. Group 2: 10 mg/kg yohimbine +25 µg/kg dexmedetomidine + ischemia/reperfusion group. Group 3: Ischemia/reperfusion (control) group. Group 4: Healthy rats. Rat ovaries were exposed to a 3-hour ischemia and then reperfusion ensured for 2 hours. After ischemia/reperfusion, total glutathione, malondialdehyde, 8-hydroxyguanine levels and histopathological investigation were studied. The highest total glutathione and the lowest malondialdehyde and DNA damage levels were determined in dexmedetomidine group when compared to control group. The difference between yohimbine + dexmedetomidine and the control group was insignificant. Dexmedetomidine protects the ovarian tissue of the rat from I/R injury. It is hypothesized that this protective effect of dexmedetomidine is mediated by the α-2 adrenergic receptors. Dexmedetomidine could be useful for attenuation of tissue damage after I/R and prevention of I/R-related complications.

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Animals; Biomarkers; Dexmedetomidine; DNA Damage; Female; Glutathione; Guanine; Ischemia; Lipid Peroxidation; Malondialdehyde; Ovary; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Yohimbine

During ischemia-reperfusion (I/R) injury in the rat kidney, apoptosis was observed in the distal tubules of the cortico-medullary region and outer medulla (OM) while severe necrosis was seen in the proximal straight tubules of the OM. The majority of these changes disappeared within 2 weeks. We examined the contents of 8-oxo-2'-deoxyguanosine (8-oxo-dG), which is a major type of oxidative damage in DNA, in the rat kidney during I/R injury, and also investigated the expression level of the OGG1 gene encoding the 8-oxoguanine DNA glycosylase. High-performance liquid chromatography with an MS/MS analysis of the nuclear DNA revealed an immediate accumulation of 8-oxo-dG in the nuclear DNA prepared from the cortex and OM of the kidney 1h after I/R, and an immunohistochemical analysis demonstrated the immediate accumulation of 8-oxo-dG in the nuclei of renal tubular cells both in the cortex and OM. A delayed increase of cytoplasmic staining with anti-8-oxo-dG was observed only in the cortico-medulla and OM, where the cytoplasmic staining in the proximal tubular cells is higher than in the distal tubular cells. The level of cytoplasmic staining representing 8-oxo-dG in mitochondrial DNA, peaked at 6h after I/R and preceded the necrosis of proximal tubular cells in the OM. An RNase protection assay showed a high level of OGG1 mRNA in the normal kidney, and the level decreased within 3h only in the OM, and increased thereafter 1-7 days of I/R both in the cortex and OM. In situ hybridization showed higher levels of OGG1 mRNA expression in the renal tubules in the OM than in the cortex of the normal kidney, which decreased rapidly within 3h of I/R. Thus, the accumulation of 8-oxo-dG in the mitochondrial DNA rather than in nuclear DNA is likely to be involved in the pathogenic responses such as necrosis of renal tubular cells during I/R injury of the kidney, together with an altered level of OGG1 expression.

Topics: Animals; Apoptosis; DNA; DNA-Formamidopyrimidine Glycosylase; Guanine; Kidney; Kidney Medulla; N-Glycosyl Hydrolases; Rats; Reperfusion Injury