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Results for “Cytoprotection”

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At least 595 records · Page 33Linked to original sources
PubMed2006

Basal rather than induced heme oxygenase-1 levels are crucial in the antioxidant cytoprotection.

Heme oxygenase-1 (HO-1) overexpression protects against tissue injury in many inflammatory processes, including ischemia/reperfusion injury (IRI). This study evaluated whether genetically decreased HO-1 levels affected susceptibility to liver IRI. Partial warm ischemia was produced in hepatic lobes for 90 min followed by 6 h of reperfusion in heterozygous HO-1 knockout (HO-1(+/-)) and HO-1(+/+) wild-type (WT) mice. HO-1(+/-) mice demonstrated reduced HO-1 mRNA/protein levels at baseline and postreperfusion. This corresponded with increased hepatocellular damage in HO-1(+/-) mice, compared with WT. HO-1(+/-) mice revealed enhanced neutrophil infiltration and proinflammatory cytokine (TNF-alpha, IL-6, and IFN-gamma) induction, as well as an increase of intrahepatic apoptotic TUNEL(+) cells with enhanced expression of proapoptotic genes (Bax/cleaved caspase-3). We used cobalt protoporphyrin (CoPP) treatment to evaluate the effect of increased baseline HO-1 levels in both WT and HO-1(+/-) mice. CoPP treatment increased HO-1 expression in both animal groups, which correlated with a lower degree of hepatic damage. However, HO-1 mRNA/protein levels were still lower in HO-1(+/-) mice, which failed to achieve the degree of antioxidant hepatoprotection seen in CoPP-treated WT. Although the baseline and postreperfusion HO-1 levels correlated with the degree of protection, the HO-1 fold induction correlated instead with the degree of damage. Thus, basal HO-1 levels are more critical than the ability to up-regulate HO-1 in response to the IRI and may also predict the success of pharmacologically induced cytoprotection. This model provides an opportunity to further our understanding of HO-1 in stress defense mechanisms and design new regimens to prevent IRI.

Animals↗
PubMed2003

Metal-chelating properties, electrochemical behavior, scavenging and cytoprotective activities of six natural phenolics.

Chelation, electrochemical, antioxidant and cytoprotective properties of six phenolics - cynarin and caffeic, chlorogenic, ferulic, protocatechuic and rosmarinic acids were studied on the following models: (i) chelation of transition metals, (ii) quenching of the diphenylpicrylhydrazyl radical (DPPH), (iii) determination of half-wave potential, (iv) erythrocytes or mitochondrial membranes damaged by tert-butyl hydroperoxide (tBH) and (v) a primary culture of rat hepatocytes intoxicated by Cu(II) and Fe(III) or tBH. All phenolics suppressed cell membrane damage induced by transition metals or tBH. The protectivity correlated with their capacity to bind transition metals, to scavenge DPPH radical and with the value of half-wave potentials. In in vitro assays, the most promising was rosmarinic acid.

Animals↗
PubMed1999

[Cytoprotection with amifostine in radiotherapy or radio-chemotherapy of head and neck tumors].

BACKGROUND: A considerable amount of experimental and clinical data prove the cytoprotective effect of amifostine on normal tissue exposed to different types of antineoplastic treatments. The present study examines its influence on the short-term toxicity of either radiotherapy alone or combined radio-chemotherapy in patients with advanced head and neck cancer. PATIENTS AND METHODS: Twenty-three patients with advanced head and neck cancer, mainly Stage III and IV, were treated with preoperative radiation (n = 1), pre- as well as postoperative radiotherapy (n = 5), postoperative radiation (n = 9) or combined postoperative radio-chemotherapy (n = 6). Before each radiation application a total dose of 500 mg amifostine was administered intravenously over 15 minutes. The documentation of this unselected patient group was compared retrospectively to a historical control group comprising 17 patients. RESULTS: In 15 patients (65%) of the amifostine group, therapy induced side effects such as mucositis and dermatitis of WHO Grade < or = 2 were detected, requiring interruptions of the radiotherapy (mean: 6.5, maximum 17 days). No mucosa or dermatologic toxicity of WHO Grade 3 or 4 was observed in this group. Significantly more acute toxicity was detected in the historical control group. Stomatitis or epitheliolysis of WHO Grade 3 occurred in 7 patients (41%). The side effects induced by the antineoplastic therapy caused an interruption of treatment in 15 patients (88%) (mean: 16, maximum 40 days; p = 0.0016). CONCLUSION: The application of amifostine before each radiation treatment seems to result in a distinct reduction of short-term toxicity of radiotherapy or combined radio-chemotherapy in patients with head and neck cancer, allowing for a better adherence to the planned radiation time schedule.

Adult↗
PubMedDate not supplied

Study of interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part II. In vitro study on the adsorption of selected spasmolytic drugs on sucralfate.

The subject of the research was the adsorption of selected musculotropic and cholinolytic spasmolytics on a cytoprotective drug--sucralfate. Adsorption evaluation was made by a static method, in vitro, the environment reaction, the concentrations of the tested drugs and the sucralfate form being taken into account. The obtained results prove that the analysed therapeutic substances are adsorbed on the sucralfate in all pH. The highest bonding capacity was observed in tests at pH=3.6, in the presence of sucralfate, which at this pH occurs in the form of suspension. The lowest capacity was at pH=1.5 in the presence of sucralfate in the paste form. In the group of the tested drugs, scopolamine butylbromide is adsorbed best, drotaverine hydrochloride little less and papaverine hydrochloride least of all.

Adsorption↗
PubMed2003

[Cytoprotective effects of amifostine in the treatment of tumors].

An efficient therapy of patients with tumorous diseases should include maximum killing of malignant cells with minimal damage to cells in healthy tissues. Radiotherapy and chemotherapy are frequently associated with a series of undesirable effects. Side effects related to the therapy may unfavorably influence quality of life for a short or long period of time, may cause the need to decrease the dosage or shorten the overall period of treatment or survival of the patient. Therefore, particular attention has recently been paid to compounds, which mitigate or eliminate the undesirable effects of the therapy. A way to decrease toxicity is the administration of radioprotective or chemoprotective compounds. The cytoprotection of healthy tissues by compounds from the aminothiol group is one of the most promising directions of research and clinical practice. Amifostin protects healthy tissue from damage induced by radio- or chemotherapy. In comparison with patients treated by radiotherapy only, radiotherapy supplemented with amifostin proved to cause significantly less acute and late untoward effects of therapy. The paper describes the possibilities of using radioprotective drugs, especially amifostin, in the therapy of tumors with particular emphasis to the needs of physicians dealing with the problems of internal medicine.

Amifostine↗
PubMedDate not supplied

Non-small cell lung cancer: the role of cytoprotection in treating therapy-related toxicity.

Concurrent radiochemotherapy improves outcomes in patients with stage III non-small cell lung cancer but produces greater toxicity, especially esophagitis and pneumonitis. Preliminary evidence suggests that cytoprotection might decrease the incidence and severity of therapy-related toxicity in these patients. In radiation-related pneumonitis, the protective effect of amifostine appears to be partly the result of a reduction in the accumulation of macrophages and a decrease in plasma and tissue tumor growth factor-beta levels.

Amifostine↗
PubMed2006

[Effect of cytoprotection on the oxidative processes and endothelial function in elderly patients with ischemic heart disease].

The aim of the study was to investigate the effects of cytoprotectional drug Mildronate ("Grindex", Latvia) on some parameters of oxidative processes and endothelial function in elderly patients with coronary heart disease (CHD). One hundred seventeen elderly CHD patients were included into controlled study. The criteria to include the patients into the study were: men and women upwards 60 years old with CHD, with heart failure FC II or III (in accord, NYHA classification), with arterial hypertension (AH), without diabetes mellitus. All patients were randomized into 2 groups: 1) 67 patients 75.4 +/- 0.5 years old were treated with Mildronate 500 mg/day against traditional basal therapy during 12 weeks (the main group) and 2) 50 patients 74.0 +/- 0.6 years old were treated only traditional basal therapy during 12 weeks (the compare group). The blood lipid profile parameters, such as total cholesterol (CH), triglycerides (TG), low density lipoprotein cholesterol (LDL-CH), high density lipoprotein CH (HDL-CH), LDL antioxidant potential (concentration of alpha-tocopherol and retinol in LDL), initial level of lipid peroxidation (LPO) products in LDL, LDL resistance to oxidation in vitro and the blood level of NO metabolites were evaluated before and after 4 and 12 weeks of the study. Effect of Mildronate on the blood lipid profile parameters in elderly CHD patients was not revealed. The initial level of LPO products in LDL was decreased and LDL resistance to oxidation in vitro was increased in main group patients after 12 weeks of study in comparison with the same parameters before the study and with compare group patients (p < 0.05). The blood level of NO metabolites was 1.5-fold higher in main group patients after 12 weeks of study in comparison with the same parameters before the study and with compare group patients (p < 0.05). Thus, in elderly CHD patients the several antiatherogenic effects of Mildronate, such as the decreasing activity of LPO processes in LDL and the increasing synthesis/secretion of blood NO, were revealed.

Aged↗
PubMed1997

Are we correctly using the inhibitors of gastric acid secretion and cytoprotective drugs? Results of a multicentre study.

AIM: To evaluate indications and frequency of prescriptions of pH-modifying and cytoprotective drugs in hospital departments. DESIGN OF THE STUDY: Multicentre cohort transverse relevation. MATERIALS AND METHODS: On a randomly selected day the clinical charts of 3685 inpatients were reviewed by a gastroenterologist and data were collected concerning the drug used, its dosage and indications for the prescription. RESULTS: 26.8% of hospitalized patients were under treatment on the day of the study. Ranitidine was the most frequently prescribed (73.9%). The purpose of treatment was cure of acute disease or symptoms in 27% of cases and prevention of peptic damage in 73%. Fear of development of stress mucosal lesions (28%) and therapy with other drugs (56%) motivated prophylactic treatment in the majority of cases. The examination of clinical charts failed to demonstrate any need for treatment in 51.4% of the patients. Disparities in the frequency of prescription between different departments and hospitals were found. CONCLUSION: Criteria used for prescription of drugs for peptic diseases in hospitalized patients should be strictly monitored to avoid excessive and unmotivated use also in general practice.

Acute Disease↗
PubMed1998

[Cytoprotective effect of ethyl esters of n-3 polyunsaturated fatty acids].

Protective properties of n-3 and n-6 polyunsaturated, monosaturated and saturated fatty acids (respectively, n-3 PUFA, n-6 PUFA, MUFA and SFA) against ethanol induced hemorrhagic gastric mucosal lesions were compared. Female Wistar rats (90-100 g) were fed to four weeks semisyntethic diets containing 9% butter (SFA-diet), 6% butter and 3% olive oil (MUFA-diet), 6% butter and 3% sunflower oil (n-6 PUFA-diet) or 6% butter and 3% concentrate of n-3 PUFA ethyl esters (n-3 PUFA-diet). One group of rats received a non-lipid diet. Under all types of lipid containing diets, development of ethanol-induced hemorrhagic gastric mucosal lesions was reduced in compared with non-lipid diet. Cytoprotective effect of n-3 PUFA-E was greater than MUFA and SFA, but smaller than n-6 PUFA.

Animals↗
PubMed1998

Application of magnetic field-induced heat shock protein 70 for presurgical cytoprotection.

To develop an alternative to hyperthermia for the induction of hsp70 for presurgical cytoprotection, we investigated the optimal exposure conditions for magnetic field induction of hsp70. Normal human breast cells (HTB124) were exposed to 60-Hz magnetic fields and hsp70 levels were measured following three different exposure conditions: continuous exposure up to 3 h, a single 20-min exposure, and a single 20-min exposure followed by repeated 20-min exposures at different field strengths. In cells exposed continuously for 3 h, hsp70 levels peaked (46%) within 20 min and returned to control levels by 2 h. Following a single 20-min exposure, the return of hsp70 levels to control values extended to more than 3 h. When cells underwent a 20-min exposure followed by repeated 20-min exposures (restimulation) with different field strengths, additional increases in hsp70 levels were induced: 31% at 1 h, 41% at 2 h, and 30% at 3 h.

Breast↗
PubMed1992

Cytoprotective effect of somatostatin in a rat model of hepatic ischemic reperfusion.

To evaluate the possible cytoprotective effect of somatostatin in hepatic ischemic reperfusion injury we used 75 adult male Wistar rats randomly separated into four groups. The rats in group 1 underwent sham operations, and those in group 2 underwent resection of the median and left lateral lobes. The rats in group 3 underwent a 90-min period of ischemia of the right lateral lobe, which we induced by temporarily occluding the right portal vein and the hepatic artery. On restoration of flow to the right lateral lobe, the median and left lateral lobes (about 80% of total liver mass) were excised (and later assayed for thymidine kinase basal activity). The rats in group 4 were given the same treatment as group 3 rats except that a saline solution of somatostatin was infused at a rate of 2 micrograms/min starting at laparotomy and lasting 24 hr. The rats in groups 1, 2 and 3 were infused with saline. Rats in groups 2, 3 and 4 were randomly assigned to two subgroups; one of these subgroups was observed until spontaneous death, and rats in the other group were killed 24 hr after the procedure for obtaining peripheral blood and liver samples. Somatostatin infusion improved the animals' survival rates from 0% (group 3) to 60% (group 4) (p < 0.05) and decreased bilirubin levels (0.78 +/- 0.17 mg/dl, n = 15 [group 4] vs. 1.69 +/- 0.04 mg/dl, n = 15 [group 3]; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response.

Calbindin is a 28 kDa calcium-binding protein expressed in restricted neuronal populations in the mammalian brain where it may play a role in protecting neurons against excitotoxic insults. Recent findings indicate that electrical activity and some neurotrophic factors can induce the expression of calbindin in neurons. We now report that brain injury, effected by systemic administration of the excitotoxin kainate or mechanical trauma, induces expression of calbindin in cells of the corpus callosum and subcortical white matter. Immunohistochemical analysis using antibodies to the astrocyte-specific proteins (glial fibrillary acidic protein and S-100 beta) established the identity of calbindin immunoreactive cells as astrocytes. Because brain injury is known to induce the expression of several neurotrophic factors and cytokines, we employed cultures of hippocampal and neocortical astrocytes to test the hypothesis that such factors can induce expression of calbindin in astrocytes. Tumor necrosis factors (TNF alpha and TNF beta), cytokines that are expressed in response to brain injury, induced the expression of calbindin in cultured rat hippocampal and neocortical astrocytes. Two neurotrophic factors, basic fibroblast growth factor and nerve growth factor, did not induce calbindin in astrocytes. TNF-treated, calbindin-expressing astrocytes were resistant to acidosis and calcium ionophore toxicity, suggesting that TNFs and calbindin may serve a cytoprotective role in astrocytes in the injured brain.

Animals↗
PubMed2003

Cytoprotective activity of Amla (Emblica officinalis) against chromium (VI) induced oxidative injury in murine macrophages.

The cytoprotective and immunomodulating properties of Emblica officinalis (Amla) against chromium (VI) induced oxidative damage are reported. Chromium (VI) at 1 micro g/mL concentration was highly cytotoxic. It enhanced free radical production and decreased reduced glutathione (GSH) levels and glutathione peroxidase (GPx) activity in macrophages. The presence of Amla resulted in an enhanced cell survival, decreased free radical production and higher antioxidant levels similar to that of control cells. Further, chromium (VI) treatment resulted in decreased phagocytosis and gamma-interferon (gamma-IFN) production while Amla inhibited chromium induced immunosuppression and restored both phagocytosis and gamma-IFN production by macrophages significantly.

Animals↗
PubMed1999

A method for determining the cytoprotective effect of catalase in transiently transfected cell lines and in corneal tissue.

Both when developing gene constructs for therapeutic purposes and when testing the biological function of proteins, it would be convenient to use cells or tissues that have been transiently transfected with the gene of interest. However, determining the protective effects of transient gene expression is complicated by a low transfection efficiency, resulting in only a minority of the cells expressing the introduced gene and consequently a reduced sensitivity of assays measuring the death of transfected cells. In this study we have developed a convenient technique for determining cell death in transiently transfected vascular endothelial cell monolayers and in corneal tissue. Vascular endothelial cells were cotransfected with human catalase cDNA and the lacZ gene encoding beta-galactosidase, under conditions in which cells expressing beta-galactosidase also expressed catalase. By assaying release of beta-galactosidase upon cell death, it was possible to show that catalase transfection led to significant protection against the cytotoxic effect of increasing concentrations of hydrogen peroxide. The assay was adapted to demonstrate the protective effects of catalase transfection on hydrogen peroxide-mediated injury of intact corneal endothelium under ex vivo culture conditions. This assay should also be useful for characterizing the cytoprotective effects of other genes in transient transfection systems.

Animals↗
PubMed1999

Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and Is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism.

We have performed cDNA sequencing and homology analyses to elucidate the complete amino acid composition for a superficial zone protein (SZP) from human and bovine cartilage which has previously been shown to be a proteoglycan specifically synthesized by chondrocytes located at the surface of bovine articular cartilage and also some synovial lining cells. The results of this study indicate that cartilage SZP is homologous with a glycoprotein first described as the precursor protein of a megakaryocyte stimulating factor (MSF). Sequence comparisons and analyses indicate that (i) the amino acid composition of SZP is highly conserved between bovine and human species, (ii) SZP contains structural motifs at the N- and C-termini which are similar to those found in vitronectin and which may impart cell-proliferative and matrix-binding properties to the molecule, and (iii) SZP contains large and small mucin-like repeat domains composed of the sequences KEPAPTTT/P (76-78 repeats) and XXTTTX (6-8 repeats), respectively, which occur within a large central region of approximately 940 amino acids. The mucin-like domains are likely to be substituted with O-linked oligosaccharides which would impart lubricating properties to SZP which in part accumulates at the articular cartilage-synovial fluid interface. Additionally, we have shown that interleukin-1 inhibits the biosynthesis of chondrocyte SZP, while TGF-beta and IGF-1 increase its biosynthesis, and that in pathological (osteoarthritic) human articular cartilage SZP mRNA can be expressed as an alternatively spliced variant lacking exons 4 and 5 which encode a potential heparin binding domain. The occurrence of different SZP alternative splice variants and the differential expression of SZP in the presence of cytokines and growth factors suggest that SZP may play an important cytoprotective role by preventing cellular adhesion to the articular cartilage surface in normal cartilage metabolism. Modifications to the structure of SZP, coupled with inhibition of SZP synthesis during inflammation, may account for the attachment and invasion of pannus observed in inflammatory joint diseases.

Amino Acid Sequence↗
PubMed1998

PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the induction of apoptosis and reverses Bcl-2-mediated cytoprotection.

One critical step of the apoptotic process is the opening of the mitochondrial permeability transition (PT) pore leading to the disruption of mitochondrial membrane integrity and to the dissipation of the inner transmembrane proton gradient (Delta Psim). The mitochondrial PT pore is a polyprotein structure which is inhibited by the apoptosis-inhibitory oncoprotein Bcl-2 and which is closely associated with the mitochondrial benzodiazepine receptor (mBzR). Here we show that PK11195, a prototypic ligand of the 18-kDa mBzR, facilitates the induction of Delta Psim disruption and subsequent apoptosis by a number of different agents,including agonists of the glucocorticoid receptor,chemotherapeutic agents (etoposide, doxorubicin),gamma irradiation, and the proapoptotic second messenger ceramide. Whereas PK11195 itself has no cytotoxic effect, it enhances apoptosis induction by these agents. This effect is not observed for benzodiazepine diazepam, whose binding site in the mBzR differs from PK11195. PK11195 partially reverses Bcl-2 mediated inhibition of apoptosis in two different cell lines. Thus, transfection-enforced Bcl-2 overexpression confers protection against glucocorticoids and chemotherapeutic agents, and this protection is largely reversed by the addition of PK11195. This effect is observed at the level of Delta Psim dissipation as well as at the level of nuclear apoptosis. To gain insights into the site of action of PK11195, we performed experiments on isolated organelles. PK11195 reverses the Bcl-2-mediated mitochondrial retention of apoptogenic factors which cause isolated nuclei to undergo apoptosis in a cell-free system. Mitochondria from control cells, but not mitochondria from Bcl-2-overexpressing cells, readily release such apoptogenic factors in response to atractyloside, a ligand of the adenine nucleotide translocator. However, control and Bcl-2-overexpressing mitochondria respond equally well to a combination of atractyloside and PK11195. Altogether, these findings indicate that PK11195 abolishes apoptosis inhibition by Bcl-2 via a direct effect on mitochondria. Moreover, they suggest a novel strategy for enhancing the susceptibility of cells to apoptosis induction and, concomitantly, for reversing Bcl-2-mediated cytoprotection.

Animals↗
PubMed1994

Evidence for cytoprotection by prostaglandin E1 with normothermic hepatic ischemia.

Although the liver is relatively resistant to normothermic ischemia, prolonged periods of inflow occlusion have produced evidence of hepatocyte injury. We have developed an animal model of liver ischemia using the pig and maintaining subtotal inflow (hepatic artery and portal vein) occlusion, allowing mesenteric portal decompression via patent portal veins through the caudate lobe, obviating the need for portosystemic shunting. This produced biochemical [aspartate transaminase (AST), lactate dehydrogenase (LDH)] and histopathologic evidence, using a microscopic grading system, of hepatocyte necrosis after 2 hr of normothermic ischemia. By administration of prostaglandin E1 (PGE1) prior to and during inflow occlusion, we have produced a statistically significant reduction in LDH (1085.9 +/- 413.5 U/liter compared to 669.1 +/- 161.4 U/liter) and AST (236.5 +/- 80.4 U/liter compared to 85.1 +/- 39.7 U/liter) (P < 0.05) between control and PGE1 animals 24 hr after reperfusion. Moreover, using the blinded microscopic grading system for hepatocellular necrosis, we have found significantly less (2.86 +/- 0.90 compared to 1.57 +/- 1.13, P < 0.01) necrosis when control and PGE1 animals were compared. Our experimental model supports the hypothesis that PGE1 exerts a cytoprotective effect during prolonged normothermic hepatic ischemia but does not aid in elucidating a mechanism for this effect.

Alprostadil↗