Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cytoprotection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed1998

Cytoprotective effects of alpha tocopherol against liver injury induced by extrahepatic biliary obstruction.

There are several important aetiologies of extrahepatic biliary obstruction (EBO). If EBO is surgically reconstructed in the critical time period, liver damage can be halted or reversed. In this golden period, lipid peroxidations significantly intensify liver defects. We hypothesised that alpha tocopherol (alpha-T) could protect the liver from the damage caused by response to EBO. In standard conditions, albino rats of Wistar strain were divided into two groups. All rats underwent double ligations and divisions of common bile ducts (CBD). One of these groups received alpha-T (CBDL-alpha-T). The other CBDL animals received intramuscular injections of normal saline (CBDL-NS). Serum samples were taken for biochemical analyses by light microscopy. The data showed a decrease in plasma bilirubin and liver enzyme levels in CBDL-alpha-T group, when compared with CBDL-NS (p < 0.05). Morphologic analyses showed better results for CBD-alpha-T. Serum levels of Malonyldialdehyd (MDA) in the CBDL-alpha-T group was 9.2 +/- 3.4 nmol/g compared to that in CBDL-NS, 12.3 +/- 4.4 nmol/g (p < 0.05). In conclusion, a dramatic protective effect of alpha-T on functional and structural features of the liver in rats with EBO was demonstrated. The data suggest that EBO may cause liver damage by stimulation of lipid peroxidation and that alpha-T may slow down liver damage in this setting.

Animals↗
PubMedDate not supplied

Cytoprotection of beta cells: rational gene transfer strategies.

Gene transfer to pancreatic islets may prove useful in preventing islet cell destruction and prolonging islet graft survival after transplantation in patients with type 1 diabetes mellitus (T1DM). Potentially, a host of therapeutically relevant transgenes may be incorporated into an appropriate gene delivery vehicle and used for islet modification. An increasing understanding of the molecular pathogenesis of immune-mediated beta cell death has served to highlight molecules which have become suitable candidates for promoting islet cell survival in the face of oxidative stress. This review aims to give an overview of some conventional gene transfer strategies aimed at promoting islet cell survival in the face of cytokine onslaught. These strategies target three aspects of islet cell physiology: redox status and antioxidant defence, anti-apoptotic gene expression and mediators of cytokine signal transduction pathways.

Diabetes Mellitus, Type 1↗
PubMed1995

The in vivo cytoprotection of ascorbic acid against ischemia/reoxygenation injury of rat liver.

The in vivo effects of ascorbic acid on the reoxygenated liver tissue were examined, with regard to the following effects: (i) the effects of scavenging radicals and/or reducing peroxidative reactions, and (ii) the effects of the chelation with low-molecular-weight iron and increasing its reactivity (radical production). Ascorbic acid is one of the water-soluble vitamins known to have various physiological effects involving both chelating and reducing properties at once. Lipid peroxidation of the reoxygenated liver tissue estimated by the production of TBARS (thiobarbituric acid-reactive substance) and LPO (lipid hydroperoxides) was suppressed effectively by the preischemic intraperitoneal administration of ascorbic acid. Ascorbic acid also showed this anti-oxidant effect in a dose-dependent manner. The analysis of the levels of ascorbic acid and glutathione of the liver tissue revealed that ascorbic acid works as an anti-oxidant probably by being oxydized finally to dehydroascorbic acid just after the reoxygenation. The latter was reduced to ascorbic acid again, coupled with the conversion of GSH to GSSG in the postischemic time course. The predominant effect of ascorbic acid on the reoxygenated liver tissue seems to be caused by the scavenging radicals and/or reducing peroxidative reactions, rather than by chelating iron and increasing its reactivity (radical production). Cellular integrity (estimated by the release of GOT, GPT, and LDH) and the energy state of the postischemic liver tissue (estimated by the tissue ATP level) were also well preserved by the administration of ascorbic acid.

Adenosine Triphosphate↗
PubMed2000

Effects of nitric oxide on the copper-responsive transcription factor Ace1 in Saccharomyces cerevisiae: cytotoxic and cytoprotective actions of nitric oxide.

Previous studies indicate that nitric oxide (NO) can serve as a regulator/disrupter of metal-metabolizing systems in cells and, indeed, this function may represent an important physiological and/or pathophysiological role for NO. In order to address possible mechanisms of this aspect of NO biology, the effect of NO on copper metabolism and toxicity in the yeast Saccharomyces cerevisiae was examined. Exposure of S. cerevisiae to NO resulted in an alteration of the activity of the copper-responsive transcription factor Acel. Low concentrations of the NO donor DEA/NO were found to slightly enhance copper-mediated activation of Acel. Since Acel regulates the expression of genes responsible for the protection of S. cerevisiae from metal toxicity, the effect of NO on the toxicity of copper toward S. cerevisiae was also examined. Interestingly, low concentrations of NO were also found to protect S. cerevisiae against the toxicity of copper. The effect of NO at high concentrations was, however, opposite. High concentrations of DEA/NO inhibited copper-mediated Acel activity. Correspondingly, high concentrations of DEA/NO (1 mM) dramatically enhanced copper toxicity. An intermediate concentration of DEA/NO (0.5 mM) exhibited a dual effect, enhancing toxicity at lower copper concentrations (<0.5 mM) and protecting at higher (> or =0.5 mM) copper concentrations. Thus, it is proposed that the ability of NO to both protect against (at low concentrations) and enhance (at high concentration) copper toxicity in S. cerevisiae is, at least partially, a result of its effect on Acel. The results of this study have implications for the role of NO as a mediator of metal metabolism.

Copper↗
PubMed1993

Cytoprotective effect of glycine in cold stored canine renal tubules.

Reperfusion injury has been suggested to cause delayed graft function in renal transplantation. Methods to reduce reperfusion injury could lead to improved clinical renal transplantation. Glycine has been shown to suppress reperfusion injury in rabbit renal tubules and rat hepatocytes. In this study we have determined the effects of glycine on viability of isolated canine renal tubules. Renal tubules were cold stored at 4 degrees C under hypoxic conditions for up to 96 h in the UW solution and rewarmed to 37 degrees C for up to 2 h under oxygenated conditions to simulate reperfusion of an organ after cold static storage. Short-term storage (24 to 48 h) did not cause membrane injury (leakage of lactate dehydrogenase (LDH)) on rewarming. However, after 72 and 96 h cold storage reperfusion injury was evident and LDH leakage increased from about 25% to 59 +/- 3% and 71 +/- 2% at 72 and 96 h cold storage, respectively. The presence of 3 mM glycine in the reperfusion medium suppressed injury to cold-stored renal tubules. After cold storage for 72 and 96 h LDH leakage was reduced to control concentrations (31 +/- 3% and 29 +/- 1%, respectively). After cold storage for 72 h there was a reduction in ATP concentration in rewarmed renal tubules (3 nmol/mg protein at 48 h to 1.25 nmol/mg protein at 72 h). Also, there was a loss of mitochondrial functions including decreased stimulation of oxygen consumption by uncoupling of oxidative phosphorylation. Although glycine suppressed LDH leakage in renal tubules cold stored for 72 h it had no effect on the regeneration of ATP or mitochondrial functions, which remained depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1998

Potential therapeutic value of drugs inhibiting semicarbazide-sensitive amine oxidase: vascular cytoprotection in diabetes mellitus.

Semicarbazide-sensitive amine oxidase (SSAO) is a copper-containing enzyme found in large amounts in blood plasma and in vascular smooth muscle. The catalytic activity of this enzyme is elevated in diabetes mellitus and some substrates, such as aminoacetone and methylamine also occur in increased amounts in this disease. After deamination by SSAO highly angiotoxic products are formed, methylglyoxal and formaldehyde, respectively. Moreover, hydrogen peroxide is also formed as a side-product. These products arising from SSAO-catalysed reactions may partially explain late-diabetic damages in the kidneys, eyes and peripheral nerves, as well as other cardiovascular disorders. It is therefore proposed that inhibition of SSAO may decrease the formation of these cytotoxic products and therefore prevent or slow the development of late-diabetic complications.

Amine Oxidase (Copper-Containing)↗
PubMed1989

Cytoprotective effect of isotonic mannitol at low oxygen tension.

The beneficial effect of mannitol infusion in postischemic kidneys remains unresolved. Contradictory reports may have originated from at least 3 different mechanisms: a) arterial vasodilation, b) osmotic support of hypoxic cellular volume regulation, and c) scavenging of hydroxyl radicals in the reoxygenation period. To exclude vascular effects we tested at 37 degrees C in hypoxic (PO2 less than 1 mmHg) and reoxygenated isolated tubular cells of rat kidney cortex cellular function, i.e. intracellular K+ accumulation (K+), posthypoxic lactate gluconeogenesis (GNG), loss of membrane-bound tau-Glutamyltransferase (tau GT), and formation of a lipid peroxidation product, malondialdehyde (MDA). Mannitol (M) was added to a Ringer incubation medium in variable concentration either without (hypertonic M) or with omission of equiosmolar amounts of NaCl (isotonic M). K+ and GNG were significantly supported, and tau GT-loss markedly suppressed in a range of 10-50 mmol/l hypertonic and isotonic M. At higher concentrations no improvement (isotonic) or even deleterious effects (hypertonic) of M occurred. Beneficial effects of lower concentrations of M (10 mmol/l) were not correlated to anaerobic glycolysis, and 1 as well as 10 mmol/l M induced a comparable and significant reduction in posthypoxic MDA-formation. This effect was most pronounced when M was only added in hypoxia, indicating leakiness of cellular membranes in hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed2000

Iron chelating, antioxidant and cytoprotective properties of dopamine receptor agonist; apomorphine.

There have been many attempts to discover neuroprotective drugs for the treatment of Parkinson's disease (PD). Many of these compounds either do not cross the blood brain barrier or are not very effective in the 6-hydroxydopamine or MPTP (N-methyl-4-phenyl-1,2,3,6-terahydropyridine) models of PD. We have examined several compounds including dopamine receptor agonist bromocritine, lisuride, pergolide and R-apomorphine for their neuroprotective action against the above neurotoxins in PC12 and dopamine neuroblastoma cell lines in culture and in vivo. R-apomorphine exhibited relatively potent neuroprotective action in vitro, cell culture and in vivo as a radical scavenger and iron chelator, because of its catechol structure. The recent clinical trials with apomorphine, where parkinsonian subjects can be weaned off L-dopa would suggest that this drug either exerts a neuroprotective action or that continuous sustained stimulation of dopamine receptor may be responsible for its unusual pharmacological activity. Apomorphine has a far more broad neuroprotective activity in the various models as compared with 1-selegiline and may therefore be an ideal drug to study neuroprotection in parkinsonian subjects with the use of PET or SPECT.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Effects of felodipine on the ischemic heart: insight into the mechanism of cytoprotection.

To assess whether the administration of felodipine protects the myocardium in a dose-dependent manner against ischemia and reperfusion, isolated rabbit hearts were infused with three different concentrations of felodipine: 10(-10), 10(-9), and 10(-8) M. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for CPK activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity; and ATP production and calcium content and tissue concentration of ATP, creatine phosphate (CP), and calcium were determined. The occurrence of oxidative stress during ischemia and reperfusion was also monitored in terms of tissue content and release of reduced (GSH) and oxidized (GSSG) glutathione. Treatment with felodipine at 10(-10) and 10(-9) M had no effect on the hearts when perfused under aerobic conditions, whilst the higher dose reduced developed pressure from 57.7 +/- 2.6 to 30.0 +/- 2.6 mmHg (p < 0.01). On reperfusion treated hearts recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. Recovery of developed pressure was 100% at 10(-8) M, 55% at 10(-9) M, and 46% at 10(-10) M. The reperfusion-induced tissue and mitochondrial calcium overload, release of CPK and noradrenaline, and oxidative stress were also significantly reduced. The effects of felodipine were dose dependent. Felodipine inhibited the initial rate of ATP-driven calcium uptake but failed to affect the initial rate of mitochondrial calcium transport. It is concluded that felodipine infusion provides dose-dependent protection of the heart against ischemia and reperfusion. Because this protection also occurred at 10(-9) M and 10(-10) M in the absence of a negative inotropic effect during normoxia and of a coronary dilatory effect during ischaemia, it cannot be attributed to an energy-sparing effect or to improvement in oxygen delivery. From our data we can envisage two other major mechanisms-(1) membrane protection and (2) reduction in oxygen toxicity. The ATP-sparing effect occurring at 10(-8) M is likely to be responsible for the further protection.

Adenosine Triphosphate↗
PubMed1991

Inability of cytoprotection to occur during a period of gastric ischemia.

Prostaglandin E2 (PGE2), colloidal bismuth subcitrate (CBS), and sucralfate (SUC) are known to protect the gastric mucosa from ethanol injury. The proposed central role for the microcirculation in gastric mucosal defense and as a site for the expression of the protective effects of these agents was investigated in the rat stomach. Animals were pretreated with either PGE2, CBS, or SUC. Control rats were given normal saline. After allowing 15 min for expression of the pretreatment, ethanol was administered as a 10%, 25%, 50%, or 100% solution to groups of rats with normally perfused stomach and to other groups of rats in whom the stomach was made ischemic by cross-clamping the supracoeliac aorta immediately prior to the instillation of ethanol. The extent of gastric mucosal damage was measured using quantitative histological techniques and expressed as a percentage of surface area and volume of mucosa damaged. In the presence of ischemia, the extent of damage by ethanol was markedly increased, with total destruction of the mucosa by the 50% and 100% solutions. With 25% ethanol, the volume of mucosal damage was increased from 0.5% in the normally perfused stomach to 53.5% with ischemia. When 10% ethanol was instilled into the ischemic stomach, only 0.8% of the volume of the mucosa was damaged, which was not different from the volume of mucosa damaged after the ischemic stomach was exposed to normal saline alone (1.0%). Pretreatment with PGE2, CBS, or SUC did not significantly change the extent of damage seen with exposure of the ischemic stomach to 25% or 50% ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗