Showing papers by "Meral Yüksel published in 1998"

Oxygen radicals and nitric oxide in rat mesenteric ischaemia-reperfusion: modulation by L-arginine and NG-nitro-L-arginine methyl ester.

Abstract: 1. The aims of the present study were to detect changes in superoxide anion (O2.-), nitric oxide (NO) and other reactive oxygen species (ROS) directly by measurement of chemiluminescence (CL) and to investigate the role of L-arginine, a nitric oxide synthase (NOS) substrate, and NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, together with their molecular enantiomers D-arginine and D-NAME, in a rat mesenteric ischaemia-reperfusion (I/R) model. 2. Seventy-nine female Wistar albino rats were divided into eight groups. The first three groups underwent sham operation; group 1 was the control group, group 2 received L-arginine and group 3 received L-NAME. Ischaemia was produced in the remaining five groups by ligation of the superior mesenteric artery for 30 min followed by 60 min reperfusion. Group 4 rats were control I/R rats and groups 5-8 received either L-arginine, L-NAME, D-arginine or D-NAME, respectively. 3. Both luminol and lucigenin CL was significantly increased in I/R groups compared with sham-operated groups. L-Arginine significantly reduced CL measurements. D-Arginine was also protective, but not as much as L-arginine. Both L- and D-arginine had in vitro O2.- (-)scavenging potential, as tested by the xanthine-xanthine oxidase system. NG-Nitro-L-arginine methyl ester decreased lipid peroxidation values in addition to reducing CL measurements. Nitric oxide concentrations were significantly increased in I/R groups in comparison with sham-operated groups. Peroxynitrite formation was increased by I/R. Treatment with L-NAME was beneficial by reducing NO concentrations in the reperfused ileum. 4. In our I/R model, O2.-, NO and other ROS were increased. Although NOS inhibitors were effective in reducing oxidative damage, increasing NO concentrations with L-arginine was also beneficial, presumably due to the ability of L-arginine to inhibit phagocyte adherence and its radical scavenging potential. In fact, NO may have different effects in terms of tissue injury or protection depending on the concentration of oxygen and the haemodynamic state of the tissue.

Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury

Abstract: Endothelins ( ETs ) are potent vasoconstrictors derived from vascular endothelium. They have primary roles in many pathophysiologic states including ischemia/reperfusion (I/R) injury. The relationships between nitric oxide (NO) and ETs are still under investigation. In this study on rats we want to focus on the interaction of NO and ET especially in I/R injury. For this purpose ET-1 and PD-156252, a nonselective ET receptor blocker, were given in a mesenteric I/R model and reactive oxygen species were detected directly using chemiluminescence of the ileal tissue. ET administrations to sham and I/R groups caused significant increases in NO concentrations whereas, in terms of peroxynitrite, which is a highly reactive group of free radicals, its increasing effects were seen only in I/R groups. This suggests that in I/R where superoxide levels increase together with NO, the conversion to peroxynitrite is likely and this effect is augmented with ET administration. On the other hand PD administration decreases superoxide and thereby peroxynitrite levels and this study shows that the effect of PD-156252 is established through this mode of action. These data suggest therapeutic approaches that may be beneficial in the treatment of I/R injury.

Adenosine protects against indomethacin-induced gastric damage in rats.

Abstract: This study examines the putativegastroprotective effect of adenosine onindomethacininduced gastric lesions and the possiblemechanisms involved. After 24 hr of starvation, the ratswere treated either with indomethacin (Indo; 25 mg/kg,subcutaneously) alone or adenosine + Indo (Ado; 7.5mg/kg, subcutaneously, three times a day), or thevehicle (5% NaHCO3, subcutaneously). Thelength of hemorrhagic lesions in the stomachs was expressed as the lesionindex. The tissue-associated myeloperoxidase (MPO)activity and protein oxidation were measured in gastrictissue samples. Formation of reactive oxygen species in gastric tissues was measured by usingluminol- and lucigenin-enhanced chemiluminescence. Inother groups of rats, gastric mucosal permeability andgastric acid output were performed following the same treatment regimens. The gastric mucosalpermeability was measured by determination of[51Cr]EDTA clearance in a perfused stomachpreparation and gastric acid secretion studies wereperformed following pylorus ligation. The lesion index, the increase inlucigenin-enhanced chemiluminescence, and the increasein gastric mucosal permeability in Indo-treated ratswere reversed by Ado pretreatment. Ado pretreatment also prevented the increase in gastric acidoutput and gastric volume in Indo-treated rats. Thus,these findings implicate that exogenous adenosine has aprotective role on indomethacin-induced gastric lesions, possibly by inhibiting gastrichyperacidity and reactive oxygen formation and bypreventing disruption of the mucosalintegrity.

Chemiluminescence Measurements for the Detection of Free Radical Species

Abstract: Reactive oxygen species (ROS) have been implicated in the pathogenesis of a variety of human diseases (Halliwell and Gutteridge, 1989). Increased appreciation of occurence of ROS, their injury potential and pathogenic role in several disease states demands quantitative methods which are diagnostic of the process and meet basic analytical criteria regarding accuracy, reliability, sensitivity and specificity (Halliwell and Grootveld, 1987). However, because of their reactive nature and short half lives, it is hard to quantitate ROS. Instead analyses of secondary or end products produced by their attack on lipids, proteins or other cellular components are preferred. These indirect methods usually give misleading results due to their poor specificity and sensitivity.

The Role of Free Radicals in NMDA and Glutamate Excitotoxicity

Abstract: The central nervous system is particularly vulnerable to oxidative stress. Neuronal membranes contain high levels of polyunsaturated fatty acids which are susceptible to free radical attack (Grisham, 1992). Normally, reactive oxygen species (ROS) generated as byproducts of cellular metabolism are maintained at very low, non-toxic levels with the aid of free radical scavengers and antioxidants (Sies, 1993). However, in recent years it has been established that oxidative stress is an important causal factor in the pathogenesis of several neurological disorders such as stroke, trauma, seizures and chronic neurodegenerative diseases (Dawson and Dawson, 1996; Simonian and Coyle, 1996).