Meral Yüksel

Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors

Several studies have shown the involvement of reactive oxygen species (ROS; O2*-, hypochlorite, hydroxyl radical, hydrogen peroxide) in carcinogenesis. With certain pathologies, nitric oxide (NO) is formed and can interact with superoxide radical (O2*-) resulting in the propagation of the highly reactive species, peroxynitrite. In order to study the molecular mechanisms underlying the ability of reactive oxygen and nitrogen species (RONS) to mediate carcinogenesis, we have measured ROS, NO, and peroxynitrite content of cancerous tissues obtained from colon and breast carcinoma cases by chemiluminescence technique. All ROS were significantly increased in cancerous colon tissues with hypochlorite making the most important contribution and suggesting the role of inflammatory cells. NO was also increased and the peroxynitrite concentration was higher in cancerous samples. For breast carcinoma cases, only O2*- was significantly increased. Hypochlorite was not detected excluding the contribution of inflammatory cells. NO concentrations were not significantly different, therefore, ROS might originate by change in the redox state of the tissue.

Lipid peroxidation and osmotic fragility of red blood cells in sleep-apnea patients

BACKGROUND Obstructive sleep apnea (OSA) refers to the occurrence of episodes of complete or partial pharyngeal obstruction with oxyhemoglobin desaturation during sleep. These hypoxia/reoxygenation episodes may cause generation of reactive oxygen species. Reactive oxygen species are toxic to biomembranes and may lead to the peroxidation of lipids. We tested the hypothesis that obstructive sleep apnea is linked to increased oxidative stress and lipid peroxidation. In order to identify target tissue/cell damage, we studied the osmotic fragility of red blood cells. METHODS Six subjects polysomnographically diagnosed as obstructive sleep apnea syndrome and 10 controls were included. After all subjects gave written informed consent, blood samples were collected in the morning between 08:00 and 09:00 a.m. following polysomnography. Blood samples were immediately transferred to the laboratory. Glutathione, lipid peroxidation and osmotic fragility of red blood cells were measured manually. RESULTS Mean glutathione and lipid peroxidation concentrations of patients were not different than those of control subjects (105.6+/-38.6 U/g Hb and 3.1+/-2.3 nmol MDA/l vs. 100.6+/-62.1 U/g Hb and 3.2+/-2.8 nmol MDA/l, respectively). In both groups, osmotic fragility of red blood cells was not changed. CONCLUSION The present study failed to support the hypothesis that obstructive sleep apnea is linked with increased oxidative stress and lipid peroxidation.

The protective effect of oxytocin on renal ischemia/reperfusion injury in rats

AIM Oxytocin was previously shown to have anti-inflammatory effects in different inflammation models. The major objective of the present study was to evaluate the protective role of oxytocin (OT) in protecting the kidney against ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS Male Wistar albino rats (250-300 g) were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (1 mg/kg, ip) or vehicle was administered 15 min prior to ischemia and was repeated immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Creatinine and urea concentrations in blood were measured for the evaluation of renal function, while TNF-alpha and lactate dehydrogenase (LDH) levels were determined to evaluate generalized tissue damage. Formation of reactive oxygen species in renal tissue samples was monitored by chemiluminescence technique using luminol and lucigenin probes. RESULTS The results revealed that I/R injury increased (p<0.01-0.001) serum urea, creatinine, TNF-alpha and LDH levels, as well as MDA, MPO and reactive oxygen radical levels in the renal tissue, while decreasing renal GSH content. However, alterations in these biochemical and histopathological indices due to I/R injury were attenuated by OT treatment (p<0.05-0.001). CONCLUSIONS Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects renal tissue against I/R-induced oxidative damage.

α-LIPOIC ACID PROTECTS AGAINST RENAL ISCHAEMIA–REPERFUSION INJURY IN RATS

1 Oxygen free radicals are important components involved in the pathophysiological processes observed during ischaemia–reperfusion (I/R). The present study was designed to assess the possible protective effect of a‐lipoic acid (ALA) on renal I/R injury. 2 Wistar albino rats were unilaterally nephrectomized and subjected to 45 min renal pedicle occlusion followed by 24 h reperfusion. Saline or ALA (100 mg/kg, i.p.) was administered 15 min prior to ischaemia and immediately before the reperfusion period. At the end of 24 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity were measured in serum samples, whereas tumour necrosis factor (TNF)‐a, interleukin (IL)‐1b, IL‐6, 8‐hydroxydeoxyguanosine (8‐OHdG) and total anti‐oxidant capacity (AOC) were assayed in plasma samples. 3 Kidney samples were taken for the determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels, as well as Na+/K+‐ATPase and myeloperoxidase (MPO) activity. The formation of reactive oxygen species in renal tissue samples was monitored using a chemiluminescence (CL) technique with luminol and lucigenin probes. Oxidant‐induced tissue fibrosis was determined by tissue collagen content and the extent of tissue injury was analysed microscopically. 4 Ischaemia–reperfusion caused a significant increases in blood creatinine, BUN, LDH, IL‐1b, IL‐6, TNF‐a and 8‐OHdG, whereas AOC was decreased. In kidney samples from the I/R group, MDA, MPO, collagen and CL levels were found to be increased significantly; however, glutathione levels and Na+/K+‐ATPase activity were decreased. Conversely, ALA treatment reversed all these biochemical indices, as well as histopathological alterations induced by I/R. 5 In conclusion, these data suggest that ALA reverses I/R‐induced oxidant responses and improves microscopic damage and renal function. Thus, it seems likely that ALA protects kidney tissues by inhibiting neutrophil infiltration, balancing the oxidant–anti‐oxidant status and regulating the generation of inflammatory mediators.

Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms

Abstract:  Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle‐treated SAH, and melatonin‐treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty‐eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood–brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+‐K+‐ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+‐K+‐ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH‐induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH‐induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema.

Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients

objective  Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.

Effects of N-acetylcysteine on myocardial ischemia-reperfusion injury in bypass surgery

Myocardial ischemia–reperfusion injury may complicate coronary artery bypass grafting (CABG) operations. N-Acertylcysteine (NAC) had antioxidant and microcirculatory effects, and inhibits neutrophil aggregation. The aim of this study was to determine the effects of NAC in limiting myocardial ischemia–reperfusion injury in CABG operations. Twenty patients undergoing elective coronary bypass operation with cardiopulmonary bypass were enrolled and randomly assigned to two groups: a control group operated with a routine CABG protocol, and one where NAC was administered intravenously during the operation (NAC group). Blood samples from coronary sinus for tumor necrosis factor-α assay, myocardial biopsy specimens for chemiluminescent luminol, and lucigenin measurements of reactive oxygen species were taken. The luminol (specific for •OH, H2O2, and HOCl− radicals) and lucigenin (specific for O2•−) levels and the difference ratios after reperfusion were significantly lower in the NAC group. Tumor necrosis factor-α levels increased in the control group but, in contrast, a significant decrease was detected in the NAC group (P < 0.01). Creatine kinase-MB levels at 6 and 12 hours were singnificantly lower in the NAC group (P = 0.02). N-Acetylcysteine has potential effects to limit ischemia reperfusion injury during CABG operations. We believe that its effects on clinical outcome may be more apparent in patients prone to ischemia–reperfusion injury.

Effect of Mitochondrial Electron Transport Chain Inhibitors on Superoxide Radical Generation in Rat Hippocampal and Striatal Slices

In this study, we have compared the generation of superoxide radical in rat hippocampal and striatal slices in the presence of specific mitochondrial electron transport chain (ETC) inhibitors (complexes I and III) under control and depolarization conditions [incubation in artificial cerebrospinal fluid (ACSF) or depolarizing ACSF (dACSF), respectively]. Superoxide radical generation was increased in both ACSF- and dACSF-incubated hippocampal and striatal slices when rotenone and antimycin A were added to the incubation medium. The increase in superoxide radical was dependent on the concentration of ETC inhibitors under control, but not depolarization conditions. Rotenone was found to be more effective than antimycin A in producing superoxide radical from hippocampal and striatal slices. Our results also showed that hippocampal slices were more sensitive to ETC inhibitors compared with striatal slices. Thus, different regions of the brain seem to differ in their capacity to generate free radicals and vulnerability to oxidative stress conditions. This difference should be considered in developing therapeutic modalities against oxidative stress-related disorders and neurodegeneration.

α-Lipoic acid modulates gut inflammation induced by trinitrobenzene sulfonic acid in rats

Background and Aim:  α‐Lipoic acid (ALA) has been shown to combat oxidative stress by quenching a variety of reactive oxygen species. It is involved in the regeneration of exogenous and endogenous antioxidants, chelation of metal ions, and repair of oxidized proteins. This study aimed to evaluate the potential beneficial effect of ALA on trinitrobenzenesulfonic acid (TNBS)‐induced gut ileitis and colitis in rats.

Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs

OBJECTIVE The aim of this study was to evaluate the effectiveness of systemic administration of resveratrol against cisplatin-induced ototoxicity in guinea pigs. MATERIALS AND METHODS Healthy guinea pigs (n=24) were randomly divided into four groups. Group 1 (n=6) received resveratrol+cisplatin, group 2 (n=6) received 4% ethanol+cisplatin, group 3 (n=6) received cisplatin, and group 4 (n=6) received saline. Cisplatin was administered at a dose of 10mg/kg/day on days 14 and 15 of the study. Resveratrol (10mg/kg/day), 4% ethanol, and saline were administered throughout the study. Baseline auditory brainstem responses (ABR) (4 kHz, 8 kHz, and click stimulus) were determined for all groups. ABR was repeated 72 h after the last dose of cisplatin in order to record the threshold shifts. The ABR threshold shifts for the click stimulus, 4-kHz- and 8-kHz-frequency stimuli were compared after drug administration. After follow-up ABRs the animals sacrificed under deep sedation and their cochleae were removed. Left cochleae were immediately harvested for measurement of level of reactive oxygen species (ROS). Right cochleae were prepared for histological changes which were observed by scanning electron microscopy (SEM). RESULTS For the all stimulus, there was a significant threshold difference among the groups (p<0.01). Group 3 had a significantly higher threshold shift at all stimuli when compared with groups 1 and 4. There was no significant threshold shifts in all stimuli between groups 2 and 3. The resveratrol-treated group 1 showed preservation of threshold in ABR (p ≤ 0.05). SEM showed that inner and outer hair cells were preserved in the group 1. Level of reactive oxygen species (ROS) were significantly higher in groups 2 and 3 compared with groups 1 and 4 (p ≤ 0.05). CONCLUSION These results indicated that systemic administration of resveratrol afforded statistically significant protection to the cochlea of guinea pigs from cisplatin toxicity. Experimental dose of resveratrol injections may have a protective effect against cisplatin ototoxicity in guinea pigs.