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Biomedical subjects

G Haklar

Publications and source records attributed to G Haklar.

28 records · Page 2Linked to original sources
PubMed1996

NMDA excitotoxicity and free radical generation in rat brain homogenates: application of a chemiluminescence assay.

NMDA, the specific agonist of glutamate gated ion channels permeable to calcium, is implicated as a causal factor in the pathogenesis of several neurobiological disorders such as stroke, seizures, ischemia, and chronic neurodegenerative diseases. On the other hand, evidence on the roles of oxidative mechanisms involved in NMDA-induced neurotoxicity is accumulating. In this study, we have used chemiluminescence measurements as an easy, rapid and sensitive assay to investigate the effects of NMDA and oxidative stress on brain cell vulnerability. Rat brain homogenates were incubated with increasing concentrations of glutamate and NMDA. Production of reactive oxygen species was followed by single photon emission measurements using the specific enhancers luminol and lucigenin. Increases in emission were observed at excitotoxic concentrations of glutamate and NMDA. Other parameters of oxidative stress such as diene conjugates, TBARS and carbonyl groups were also investigated. Our results indicated that chemiluminescence measurements may be used to study involvement of oxidative stress in neurotoxicity.

Acridines↗
PubMed1996

Involvement of free radicals in the cardioprotective effect of defibrotide.

Ischemia followed by reperfusion has deleterious effects on myocardial tissue and a wide range of drugs have been investigated to modulate these changes. Defibrotide (polydeoxyribonucleotides from bovine lung), a drug with antithrombotic and fibrinolytic activities, has also proven to be cardioprotective against myocardial ischemia/reperfusion damage. However, the mechanism of this protective effect has not been clarified yet. The aim of this study was to determine whether this effect is due to protection against free radical induced changes. The experimental model in rabbits includes coronary artery ligation for 60 min followed by a reperfusion period of 45 min. In this model, free radical damage was estimated by different parameters of lipid peroxidation such as diene conjugation, carbonyl content, and thiobarbituric acid reactive substances, together with protein oxidation determinations. The results demonstrate that defibrotide prevents free radical induced changes after myocardial ischemia/reperfusion.

Animals↗
PubMed1995

Evaluation of oxidant stress in chronic hemodialysis patients: use of different parameters.

Patients with chronic renal failure, particularly those undergoing regular dialysis treatment (RDT) are candidates for free radical damage. It is difficult to quantitate free radicals because of their short half-lives and reactive nature. Therefore, indirect methods measuring products of lipid peroxidation and protein oxidation are preferred. The present study displays a profile of lipid peroxidation and protein oxidation parameters, which are more sensitive and specific than the widely used method measuring thiobarbituric acid reactive substances (TBARS), adapted to the plasma and erythrocyte samples of RDT patients. We have observed increased levels of plasma and erythrocyte lipid peroxidation and also demonstrated increased protein oxidation in erythrocyte membranes of RDT patients.

Blood Proteins↗
PubMed1995

The effects of experimental splenic autotransplantation and imipenem-cilastatin treatment in postsplenectomy Pseudomonas aeruginosa sepsis.

Male Wistar albino rats were allocated to three groups-sham operated (n: 10), splenectomized (n: 20) and splenic autotransplanted (n: 10). Twelve weeks after operation, all were challenged with 1.8 x 10(8) cfu/ml Pseudomonas aeruginosa intranasally. Half of the splenectomized rats received imipenem-cilastatin after 2 h of bacterial challenge. Mortality was then observed for the next 12 days. All animals were autopsied and liver, kidney, spleen and lung specimens were processed for microbiological culture and histopathological examination. In 80% of autotransplanted rats, splenic tissue regeneration was histopathologically verified. Hemoglobin oxidation of erythrocytes increased in splenectomized rats and remained close to control levels in the autotransplanted group. No significant difference was detected between IgM levels of splenectomized and autotransplanted groups. Mortality rates were the same for all groups, except that splenectomized animals given antimicrobial therapy had increased survival rates. In conclusion, it is likely that the spleen has no role in protection against pulmonary sepsis and that only appropriate antimicrobial therapy can protect the splenectomized host from Pseudomonas sepsis.

Animals↗
PubMed1995

Protective effects of cilazapril against free radical injury in myocardial ischaemia-reperfusion.

Cilazapril is a prodrug which is rapidly hydrolysed to the pharmacologically active cilazaprilat following absorption to the bloodstream. In clinical pharmacological studies, administration of cilazapril resulted in potent, reversible, selective and competitive angiotensin converting enzyme inhibition. In this study, we have examined the protective effect of cilazapril on a myocardial ischaemia-reperfusion model by using different parameters of lipid peroxidation and protein oxidation. We have observed increased levels of diene conjugates, carbonyls and malondialdehyde as well as protein carbonyls after ischaemia-reperfusion, whereas protein sulphydryl groups were decreased. Our results clearly demonstrate that cilazapril, a non-sulphydryl, long-acting angiotensin converting enzyme inhibitor, has free-radical-scavenging potential in a model comparable to the clinical situation observed in humans.

Animals↗
PubMed1994

Captopril increases endothelin serum concentrations and preserves intestinal mucosa after mesenteric ischemia-reperfusion injury.

Endothelial cells modulate the tone of the underlying smooth muscle by generating endothelium-derived relaxing and constricting factors. Captopril (CPT), unlike other angiotensin-converting enzyme (ACE) inhibitors, contains a sulfhydryl (-SH) group and can act as a free radical scavenger. Iloprost (ILO) is a synthetic analogue of prostacyclin and mimics the effects of this compound. This study was designed to investigate the effect of ILO and CPT on the mechanism of endothelin (ET) release after mesenteric ischemia-reperfusion (I/R) injury in the rat. Sprague-Dawley rats were divided into five groups: sham-operated, control, ILO (25 micrograms/kg), CPT (10 micrograms/kg), and ILO + CPT. The superior mesenteric artery was occluded for 30 min and then allowed 90 min of reperfusion, except in the sham-operated group, and the corresponding agents were given to the treated groups prior to I/R injury. After I/R injury, portal venous blood was obtained for ET assay, and ileal tissue samples were also obtained for the determination of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) and for histopathological examination. MDA levels were significantly lower in the CPT, ILO and, ILO + CPT groups than in the control group, indicating the inhibition of lipid peroxidation in all groups. ET levels increased in the control group, and this increase was reversed with ILO. In the CPT group, ET levels were significantly increased, and the addition of ILO did not affect this increase. Significant cytopreservative effect was achieved with ILO and CPT, the latter being more prominent histopathologically. CPT exerts a significant protective effect on the intestinal mucosa after I/R injury. This protection is accomplished by increased ET levels and seems to be unrelated to its inhibitory effect on lipid peroxidation and also unrelated to the arachidonic acid cascade.

Animals↗
PubMed1994

Does PGE2 act as a mediator for endothelin release?

To investigate the effect of iloprost (ZK 36374) and thromboxane synthetase inhibitor UK 38485 on endothelin release by the intestinal vascular endothelium after ischemia/reperfusion (IR) injury, five experimental groups were formed. The groups consisted of sham, control, iloprost treated (ILO), UK 38485 treated (TSI), and iloprost + UK 38485 treated (ILO + TSI) groups. The last three groups received the corresponding agents and then the superior mesenteric artery was clamped for 30 min followed by 90 min reperfusion. Endothelin levels in the portal blood and malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) levels in the intestinal tissue were determined. The MDA levels increased significantly in the control group and this increase was reversed in ILO, TSI, and ILO + TSI groups, the two drugs together showing a synergistic effect in preventing lipid peroxidation. The changes in the LTC4 levels were not significant among the groups. The increased endothelin levels in the control group were reversed in ILO and TSI groups but these two agents did not have a synergistic effect. Increased PGE2 levels were reversed with iloprost but neither UK 38485 nor the combination of the two agents was effective in decreasing PGE2 levels. It is concluded that endothelin release after mesenteric IR injury is relatively unrelated to lipid peroxidation and the lipoxygenase pathway. The cylooxygenase pathway has a direct effect on endothelin release and PGE2 may act as a mediator.

Animals↗
PubMed1994

Effect of verapamil and iloprost (ZK 36374) on endothelin release after mesenteric ischemia-reperfusion injury.

In this experimental study we studied the effect of verapamil and iloprost on endothelin release in ischemia/reperfusion (IR) injury of the rat intestine. Endothelin levels in the portal blood and malondialdehyde (MDA), PGE2, and LTC4 levels in the intestinal tissue were determined. The MDA levels increased in the control group and this increase was reversed with iloprost, verapamil and both. The change in the LTC4 levels was insignificant between the groups. Iloprost reduced PGE2 and endothelin release, but verapamil was not as effective and no synergistic effect was encountered. The increased PGE2/LTC4 ratio was also reversed in the experimental groups, verapamil being less effective. Endothelin release seems to be related to both PGE2 levels and the PGE2/LTC4 ratio after mesenteric IR injury.

Animals↗
PubMedDate not supplied

Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury (II).

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.

Acridines↗