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 145 records · Page 8Linked to original sources
PubMed1986

Gastric cytoprotection of aceglutamide aluminium in rats.

Aceglutamide aluminium (AGA, KW-110, Glumal) at doses of 30-100 mg/kg p.o. prevented the formation of the gastric lesions induced by three noxious compounds, ethanol, HCl and acidified taurocholate, all dose-dependently. The preventive effect of AGA against taurocholate-induced lesions was more marked than that against the other two noxious agents. AGA at the cytoprotective doses caused almost no decrease of the gastric acid secretion in both pylorus-ligated and non-ligated rats. AGA stimulated gastric mucus secretion and prevented the increment of back-diffusion of hydrogen ion into the mucosa significantly. These data indicate that AGA caused a cytoprotective effect not through the suppression of acid secretion but through the augmentation of the defense of the mucosa against autodigestion by gastric juice. In addition, pretreatment with indomethacin diminished the cytoprotective effect of AGA almost completely. This result suggests that the mechanisms of AGA's cytoprotection may be concerned with endogenous prostaglandins.

Administration, Oral↗
PubMed1985

Gastric cytoprotective, antisecretory and antiulcer activities of (E)-4-oxo-4-(3,4,5-trimethoxyphenyl)-2-butenoic acid (RU 38086).

As a result of trials of a large series of compounds, RU 38086 (E)-4-oxo-4-(3,4,5-trimethoxyphenyl)-2-butenoic acid) was selected because of its cytoprotective, antisecretory and antiulcer properties. In pylorus-ligated rats, RU 38086 dose-dependently decreased the total acid output, at 2.5, 5 and 10 mg/kg orally and at 10 and 50 mg/kg intraduodenally. In the perfused rat stomach, 1.2 mg/kg RU 38086 in situ inhibited acid secretion stimulated by histamine or pentagastrin but was inactive against carbachol. In the same test 5 mg/kg intravenously did not antagonize pentagastrin-induced acid secretion. In the cat Heidenhain pouch, 0.6 mg/kg RU 38086 was also antisecretory, reducing the acid concentration when in contact with the mucosa of the pouch. In ulcers induced in rats by ligature of the pylorus plus acetylsalicylic acid, RU 38086 at 2.5 and 5 mg/kg demonstrated much more striking activity after oral than after intraduodenal administration. It also had antiulcer activity against stress ulcers (restraint plus cold), starting at a dose of 5 mg/kg orally. RU 38086 had marked gastric cytoprotective activity in rats against the necrotizing effects of ethanol from the low dose of 0.3 mg/kg orally. This cytoprotective activity was not significantly affected by indomethacin pre-treatment. At 4 and 20 mg/kg orally, RU 38086 strongly increased prostaglandin E2 levels in gastric juice of pylorus-ligated rats and in stomach tissue of normal rats. These data indicate that RU 38086 is an orally effective cytoprotective, antisecretory and antiulcer agent.

Animals↗
PubMed1979

Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury.

Oral administration to fasted rats of either absolute ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, 25% sodium chloride, or boiling water produced extensive necrosis of the gastric mucosa. Pretreatment with several prostaglandins of the A, E, or F type, either orally or subcutaneously, prevented such necrosis, and the effect was dose-dependent. This property of prostaglandins is called "cytoprotection." The protective effect against oral administration of absolute ethanol was already maximal 1 min after PGE2 given orally, and 15-30 min after PGE2 given subcutaneously. Cytoprotection by prostaglandins is unrelated to the inhibition of gastric acid secretion since, (a) it is maximal at doses that have no effect on gastric secretion, and (b) anti-secretory compounds (cimetidine, methscopolamine bromide) and antacids are not cytoprotective. Although the mechanism of gastric cytoprotection is unknown, prostaglandins appear to increase the resistance of gastric mucosal cells to the necrotizing effect of strong irritants. These results suggest that certain prostaglandins, by a mechanism other than the inhibition of gastric acid secretion, maintain the cellular integrity of the gastric mucosa, and might be beneficial in the treatment of a variety of diseases in which gastric mucosal injury is present.

Animals↗
PubMed1981

Gastric cytoprotection by prostaglandins, ranitidine, and probanthine in rats. Role of endogenous prostaglandins.

Intragastric administration of aspirin (ASA) plus 0.15 M HCl to fasted rats produced typical gastric ulcers accompanied by almost complete disappearance of mucosal prostaglandins (PGs). Pretreatment with various exogenous PGs that were biologically inactive (e.g. 6-keto-PGF1 alpha or PGF2 beta) or active (PGE2 and PGI2) but used in non-antisecretory doses prevented the formation of these gastric lesions ('cytoprotection'). Besides PGs, antisecretory compounds such as ranitidine, a new H2-receptor antagonist, and probanthine were also found to be cytoprotective, even when given in non-antisecretory doses. Mucosal generation of PGs in animals treated with ASA and HCl plus ranitidine or probanthine was very low and not significantly different from those receiving only ASA and HCl. Thus, the cytoprotection appears to be the property not only of PGs but also of conventional gastric antisecretory compounds such as H2-receptor antagonists or anticholinergics. This cytoprotection can be demonstrated under conditions excluding any role of gastric secretory inhibition and in the absence of endogenous PGs.

Animals↗
PubMed1983

Studies on the mechanisms of the antisecretory and cytoprotective actions of SCH 28080.

The antisecretory and cytoprotective actions of SCH 28080 (2-methyl-8-(phenylmethoxy)imidazol[ 1,2-a ]pyridine-3-acetonitrile), an antiulcer compound, were characterized. In the isolated guinea-pig gastric mucosa, SCH 28080 at 5 X 10(-8) M abolished the acid secretory responses to histamine and methacholine but at 5 X 10(-7) M also inhibited the responses to dibutyryl cyclic AMP plus theophylline. The data suggest that the antisecretory effect of SCH 28080 involves a direct action on the parietal cells distal to the primary events mediating the cholinergic and H2 histaminergic secretory mechanisms. In the histamine-stimulated dogs, a prolonged suppression of acid secretion was accompanied by only a transient fall in the ratio of mucosal plasma flow to acid output after i.v. dosing of SCH 28080, 1 mg/kg, indicating that the antisecretory action of SCH 28080 was not secondary to changes in gastric blood flow. Mechanisms mediating the cytoprotective effects of SCH 28080 were investigated. SCH 28080 (10 mg/kg p.o.) increased total mucus as determined by measurements of N-acetylneuraminic acid in rat stomach. In the isolated guinea-pig gastric mucosa, bicarbonate secretion was augmented in a dose-dependent (10(-6)-10(-4) M) manner. Concomitant stimulation of the gastric mucus and bicarbonate by SCH 28080 may lead to strengthening of the gastric mucosal barrier and account for its gastric cytoprotective activity against injuring agents. In conclusion, the antisecretory and cytoprotective activities of SCH 28080 are due to a direct action on the parietal cells and a stimulatory effect on mucus and bicarbonate secretion by the mucosal epithelial cells, respectively.

Animals↗
PubMed1984

Interrelationships between the development of the gastric cytoprotective effects of prostacyclin, atropine, cimetidine and the gastric mucosal superoxide dismutase activity in rats.

Gastric mucosal damage was produced by the intragastric administration of 96% ethanol or 0.6 M HCl. The cytoprotective doses of prostacyclin (PGI2) (5 micrograms/kg), atropine (0.025 mg/kg) or cimetidine (2.5 mg/kg) were given intraperitoneally 30 min before the administration of the necrotizing agents. The animals were killed 1 hr later. The number and severity of gastric mucosal lesions (ulcer) were recorded. At the time of the sacrifice of the animals, superoxide dismutase (SOD) was prepared from the gastric fundic mucosa and its activity was measured. It was found that PGI2 (5 micrograms/kg), atropine (0.025 mg/kg) and cimetidine (2.5 mg/kg) significantly decreased the number and severity of gastric mucosal lesions (ulcers) produced by the intragastric administration of 96% ethanol a 0.6 M HCl, PGI2, atropine, cimetidine, given in cytoprotective doses, significantly mounted the ethanol-induced increase of gastric mucosal SOD activity; PGI2, atropine, cimetidine, given them in cytoprotective doses significantly shunted the HCl-induced decrease of gastric mucosal SOD activity. It has been concluded that; chemically different cytoprotective agents (PGI2, atropine, cimetidine) give rise to similar tendencies in the changes of gastric mucosal SOD activity; both the significant decrease (in the ethanol-model) and the significant increase (in the HCl-model) of this enzyme seem to be involved in the development of gastric mucosal protection by PGI2, atropine and cimetidine.

Animals↗
PubMed1984

Lack of correlation between mucus gel thickness and gastric cytoprotection in rats.

The effect of various cytoprotective agents on the thickness of gastric mucus gel layer in rats was studied. It was hypothesized that an increase in the mucus gel layer might be involved in cytoprotection. The results show that this is not the case. Neither prostaglandin E2, 16,16-dimethyl prostaglandin E2, nor mild irritants (20% ethanol, 0.35 M HCl, 20% glucose, 20% mannitol), all given orally, altered the thickness of the mucus gel layer, although these agents were found to be cytoprotective, i.e., inhibiting the formation of gastric mucosal necrotic lesions caused by oral administration of absolute ethanol. The only agents that significantly increased the thickness of the mucus gel layer were a hypertonic solution (4% NaCl) and sodium salicylate. We conclude that if mucus plays a role in cytoprotection, it is not by virtue of an increase in thickness of the gel layer adherent to the gastric mucosa.

Animals↗
PubMed1983

Cytoprotecting-effect of cimetidine: experimental evidence in the rat gastric mucosal lesions induced by intragastric administration of necrotizing agents.

Contradictory data have been found on cimetidine-induced gastric cytoprotection. In our paper the effect of cimetidine administered intraperitoneally in doses of 2.5, 10 and 50 mg X kg-1, on: 1. The gastric acid secretory responses in 1 and 4 hr pylorus-ligated rats, and 2. The rat gastric mucosal lesions induced by intragastric administration of 0.6 M HCl, 0.2 M NaOH, 96% ethanol and 25% NaCl is discussed. It was found that: 1. Cimetidine dose-dependently inhibited the gastric acid secretion in 1 and 4 hr pylorus-ligated rats, but a dose of 2.5 mg X kg-1 did not exert any significant inhibition; 2. All doses of cimetidine significantly prevented the gastric lesion development induced by different necrotizing agents (0.6 M HCl, 0.2 M NaOH, 96% ethanol, and 25% NaCl); 3. The cytoprotecting dose of cimetidine was of 2.5 mg X kg-1; and 4. The duration of cimetidine-induced cytoprotection was 1 hr long before the administration of the necrotizing agent. These results suggest a real cimetidine-induced gastric cytoprotection.

Animals↗
PubMed1983

Gastric antisecretory and cytoprotective activities of SCH 28080.

SCH 28080 (2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile) is a novel antiulcer agent which has both antisecretory and cytoprotective activities. The antisecretory ED50 values in the pylorus-ligated rat were 3.7 mg/kg p.o. and 2.8 mg/kg i.p., being 7 and 10 times more potent than cimetidine, respectively. In dogs, SCH 28080 was effective in inhibiting acid secretion stimulated by histamine (ED50 of 0.09 mg/kg i.v. and 4.4 mg/kg p.o.), dimaprit, pentagastrin, insulin and feeding. The cytoprotective activity of SCH 28080 was demonstrated by inhibition of ethanol-induced gastric lesions in a dose-dependent manner in rats (ED50:3.0 mg/kg p.o.). SCH 28080 was active in similar dose ranges (1-10 mg/kg) by both p.o. and i.v. routes of administration. This gastric cytoprotective activity was not affected by indomethacin pretreatment. Furthermore, the gastric potential difference was effectively sustained by SCH 28080 (3, 10 and 30 mg/kg p.o.) after intragastric ethanol. SCH 28080 (1-30 mg/kg p.o.) also inhibited gastric ulcers provoked by aspirin, aspirin + acid, indomethacin and stress (cold-restraint) in rats. The data support the concept that it is possible to have combined antisecretory and cytoprotectant actions in a single molecule which is not a prostaglandin.

Animals↗
PubMed1995

Adaptive cytoprotection by ammonia and urea-urease system in the rat gastric mucosa.

Urease and ammonia (NH4OH) have been proposed to be play a major role in the pathogenesis of the the Helicobacter pylori (Hp)-associated gastric damage but the mechanism of this damage has not been fully explained. This study was designed the determine whether topical application with NH4OH at low concentration or the generation of the NH4OH in gastric lumen by the hydrolysis of urea in the presence of urease can induce adaptive cytoprotection. Single insult of NH4OH alone in various concentrations (15-500 mM) caused the mucosal damage starting at 30 mM and reaching at 250 mM the value similar to that obtained with 100% ethanol and being accompanied by the fall in gastric blood flow to about 30% of the normal value. When the mucosa was first exposed to the low concentration (15 mM) of NH4OH, causing by itself only small microscopic damage of surface epithelium, but then insulted by a high concentration (250 mM) of NH4OH, the extent of mucosal damage was greatly attenuated as compared to that caused by NH4OH alone. This "adaptive" cytoprotection, accompanied by the rise in the GBF, was reversed in part, after the pretreatment with indomethacin to inhibit PG-cyclooxygenase, with L-NAME to suppress NO-synthase or with capsaicin to induce deactivation of sensory nerves. The combined topical pretreatment with urea (2%) and urease (100 U) to generate NH4OH in the stomach, also significantly reduced the severity of gastric lesions induced by 100% ethanol and this was also accompanied by a significant rise in the gastric blood flow. The protective and hyperemic effects of urea and urease were significantly attenuated by the pretreatment with indomethacin or suppression of NO-synthase by L-NAME. The functional ablation of sensory nerves by the pretreatment with capsaicin also reversed, in part, the protective effect of the combination of urea plus urease and abolished completely the mucosal hyperemia accompanying this protection. We conclude that 1) NH4OH alone at higher concentrations damages the gastric mucosa but when applied at lower concentration corresponding to that in the stomach of Hp-infected patients, or generated by the urea in the presence of urease, NH4OH acts like "mild irritant" to induce adaptive cytoprotection, 2) this adaptive cytoprotection is mediated, in part, by endogenous PG, sensory nerves and arginine-NO-dependent pathway.

Adaptation, Physiological↗
PubMed1996

The cytoprotective effect of leminoprazole on indomethacin-induced damage to rabbit gastric mucosal cells.

Leminoprazole (an acid pump inhibitor) has a mucosal protective effect against various experimental gastric lesions, but the underlying mechanism remains unknown. We examined whether leminoprazole prevents indomethacin-induced damage to cultured gastric mucosal cells. The viability of rabbit gastric mucosal cells was assessed by the 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide and dye exclusion methods. [35S]Methionine-labeled proteins were detected by autoradiography after sodium dodecylsulfate-polyacrylamide gel electrophoresis. Western blot analysis was carried out using anti-heat shock protein (HSP)-70 and anti-HSP-72 antibodies. Exposure of gastric mucosal cells to indomethacin for 4 hr apparently reduced their viability in a dose-related manner. Pretreatment with leminoprazole for 4 hr significantly prevented the reduction in cell viability caused by 50 microM indomethacin, although omeprazole was not effective. However, such pretreatment did not prevent the severe damage induced by 500 microM indomethacin. 16,16-Dimethyl prostaglandin E2 significantly prevented the cell damage induced by indomethacin at both 50 and 500 microM. Leminoprazole alone did not affect cell viability. The cytoprotection by leminoprazole was expressed after a 2-hr lag period. Leminoprazole did not promote prostaglandin E2 synthesis by cells, but it apparently induced the synthesis of 83-kDa, 72-kDa, 52-kDa and 35-kDa proteins. Both the cytoprotection and the induction of such protein synthesis were abolished by cycloheximide and actinomycin D. The leminoprazole-induced 72-kDa protein did not react with the antibodies against HSP-70 and HSP-72. These results indicate that leminoprazole directly protects gastric mucosal cells against mild damage caused by indomethacin and that its cytoprotective effect might be mediated through de novo synthesized proteins. In addition, it is suggested that the leminoprazole-induced proteins might be unknown proteins related to cytoprotection, although the exact characters of the proteins are unclear.

16,16-Dimethylprostaglandin E2↗
PubMed1996

[The cytoprotective effect of magnesium in global myocardial ischemia].

BACKGROUND: Administration of magnesium in the therapy of ischaemic heart diseases does not belong to the standard procedures. The results of clinical trials with application of this cation are mutually contradictive, mechanisms of its effect are not solved yet. Many physicians consider magnesium to represent a classical placebo, or an uncertain light sedative. MAIN PURPOSE AND OBJECTIVES: The study is aimed at proving the direct effect of magnesium on the heart muscle under ischaemic conditions which exclude the placebo effects. These conditions are mostly fulfilled by the model of isolated heart. MATERIAL AND METHODS: The authors used isolated rabbit hearts according to Langedorff with Krebs-Henseleit (KH) perfusion solution, the only variable of which is represented by concentration of magnesium. The following groups of patients were formed: 1. Control group-30-minute perfusion with normal Mg concentration (0.5 mmol/l) in KH solution. 2. Hypomagnesemia-30-minute perfusion with KH solution Mg-free. 3. Normomagnesemia+ischaemia-30-minute perfusion with normal concentration succeeded by a 60-minute global ischaemia. 4. Hypomagnesiaemia+ischaemia-30-minute perfusion with KH solution magnesium-free succeeded by a 60-minute global ischaemia. 5. Hypermagnesiemia +ischaemia-30-minute perfusion with increased Mg concentration in KH solution to 2.0 mmol/l succeeded by a 60-minute global ischaemia. The investigated parameters: after completion of perfusion the authors isolated mitochondria and evaluated individual parameters of oxidative phosphorylation by means of oxygraph/Gilson/with Clark's oxygen electrode. The calcium uptake by mitochondria was observed by means of calcium-sensitive electrode Orion (oxygraph Gilson). The formation of free oxygen radicals was observed indirectly by spectrophotometric assessment of malondialdehyde production. Concentration of mitochondrial nucleotides (AMP, ADP, ATP) was assessed by using HPLC. RESULTS: Hypomagnesemia lasting 30 minutes had a negative effect on the index of oxidative phosphorylation (ADP:O p < 0.005) the uptake of calcium (p < 0.002), ATP concentration in mitochondrial ATP (p < 0.05) and the production of free radicals significantly increased (p < 0.001). Normomagnesemia indicated practically no cytoprotective effect before global ischaemia of myocardium lasting for 60 minutes. Hypermagnesemia indicated a direct cytoprotective effect before global ischaemia affecting respiration of isolated heart mitochondria in state of S3 (p < 0.001), respiration control index RCI (p < 0.001), the rate of oxidative phosphorylation OPR (p < 0.001) and on the index of oxidative phosphorylation ADP:O (p < 0.05) on the uptake of calcium by mitochondria (p < 0.002) and on concentration of mitochondrial nucleotides ATP (p < 0.002). It was remarkable that also under conditions of moderate hypomagnesemia the production of malondialdehyde increased. CONCLUSIONS: Under our experimental conditions it was confirmed that magnesium yields direct cytoprotective effect on the subcellular level of the myocardium prior to global ischaemia, providing the process takes place under the condition of hypermagnesemia. (Tab. 1, Fig. 12, Ref. 45.) Key words: hypomagnesemia, normomagnesemia, hypermagnesemia, Langendorff's global ischaemia, mitochondrial metabolism, cytoprotective effect.

Adenosine Triphosphate↗
PubMed2003

Role of MAPK phosphorylation in cytoprotection by pro-vitamin C against oxidative stress-induced injuries in cultured cardiomyoblasts and perfused rat heart.

The reactive oxygen species (ROS) are known to be generated upon post-ischemic reperfusion (I/R) of the heart, and to injure cardiac muscle cells. The hydrogen peroxide-induced mortality of rat cardiomyoblasts H2c9 was markedly inhibited by previous administration with auto-oxidation-resistant pro-vitamin C, the 2-O-phosphorylated derivative (Asc2P) of ascorbic acid (Asc). The cytoprotection was partially counteracted by an inhibitor of MAPK (mitogen-activated protein kinase) kinase (MEK) as shown by DNA strand cleavage assay and mitochondrial dehydrogenase assay. Immunostains indicated that phosphorylated MAPK increased in the hydrogen peroxide-treated cardiomyoblasts, and that this action was moderately inhibited by Asc2P and restored nearly to the initial, pretreatment level by combined administration of the MEK inhibitor and Asc2P. The I/R-induced cell injuries in perfused rat hearts as estimated by extracellular release of the cardiac enzyme CPK were inhibited by 2-O-alpha-glucosylascorbic acid (Asc2G) and Asc, whereas the observed cytoprotection for the cardiomyoblasts was partially counteracted by the MEK inhibitor. The increase in phosphorylated MAPK in I/R-operated hearts was moderately inhibited by pro-vitamin C, but restored nearly to the normal non-operated level by combined administration with the MEK inhibitor. This is in contrast to no alteration in levels of non-phosphorylated MAPK for all the cases examined as shown by Western blots, consistent with results of immunostains for the cardiomyoblasts. The inhibitory effect of the MEK inhibitor on MAPK phosphorylation was, therefore, suggested to counteract the cytoprotective effects of pro-vitamin C via a thorough interruption of the phosphorylated MAPK signaling pathway. This was not true of ROS-related events; the scavenging effects of Asc2G and Asc on hydroxyl radicals generated from I/R-operated heart were not affected by combined administration with the MEK inhibitor, as shown by the spin-trapping DMPO-based ESR method.

Aldehyde Dehydrogenase↗
PubMed2000

Cytoprotective mechanism of heat shock protein 70 against hypoxia/reoxygenation injury.

The role of heat shock protein 70 (HSP70) in the cytoprotection against hypoxia/reoxygenation injury was examined. Adult rat cardiomyocytes were isolated, subjected to hyperthermia at 42 degrees C for 15 min (heat shock treatment), and then incubated at 37 degrees C for 3 to 24 h (HSP production process). Heat shock treatment increased HSP70 production (80-260% increase); the peak increase was seen after 9 h of HSP production process. Thereafter, the cells were subjected to 120-min hypoxia and 15-min reoxygenation. Heat shock treatment increased the survival of the cells subjected to hypoxia/reoxygenation (1.5-2.5-fold); the maximal cytoprotection was observed after 12 h of HSP production process. Heat shock treatment increased HSP70 content in the nucleus when cells were subjected to 12 h of HSP production process. To examine the role of HSP70 accumulation in the nuclear fraction, the activity of poly(ADP-ribose) synthetase (PARS), which functions in the nucleus and consumes high-energy phosphates excessively in the reoxygenated state, were measured in the cells with heat shock and 12 h of HSP production process. Heat shock treatment attenuated the hypoxia/reoxygenation-induced increase in the PARS activity (50% decrease). Treatment of the cells with 3-aminobenzamide, an inhibitor of PARS, exerted the effects similar to those of heat shock treatment. These results suggest that attenuation of the PARS activity in the nucleus may play an important role in the cytoprotective effect of HSP70 on hypoxia/reoxygenation injury.

Animals↗
PubMed1999

Cytoprotection against lipid hydroperoxides correlates with increased glutathione peroxidase activities, but not selenium uptake from different selenocompounds.

Cells cultivated under standard conditions were highly deficient in tocopherol, selenium, and glutathione peroxidase (GPx) activities. We investigated whether and to what extent the addition of different selenocompounds to growth media would alter biochemical, physiological, and pathophysiological parameters of cultured liver cells. Cellular uptake of selenium, GPx activities, and cytoprotection were measured and compared in human hepatoma cells (HepG2). Selenite and selenocystine were Se donors of high bioavailability (i.e., with these culture supplements, the increased Se uptake, induction of GPx isoenzymes, and protection of treated cells from lipid hydroperoxides were well correlated). In contrast, selenium from selenomethionine was incorporated into cellular proteins but had no effect on GPx activities or cytoprotection. The data show that not all selenium donors provide selenium, which is bioactivated to act as antioxidant. Thus, cellular selenium content, in general, did not correlate with cytoprotective activity of this trace element. However, cellular GPx activities at different times, with different concentrations, and with different Se donors always correlated with protection from lipid hydroperoxides and may, thus, represent a more reliable parameter to define adequate Se supply.

Antioxidants↗
PubMed2005

Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages.

The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 microg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities.

Antioxidants↗
PubMed2005

Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins.

Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson's disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, gammaGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K-Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD.

Antioxidants↗
PubMed2006

The water-soluble fullerene derivative "Radical Sponge" exerts cytoprotective action against UVA irradiation but not visible-light-catalyzed cytotoxicity in human skin keratinocytes.

Fullerene was entrapped in polyvinylpyrrolidone of 60-80 kDa at a molar ratio range of 0.42-0.67:1, resulting in a water-soluble derivative with a mean particle diameter of about 688 nm, named "Radical Sponge" because of its ROS-scavenging ability as previously demonstrated, and examined in the present study for its photo-biological actions toward human skin keratinocytes HaCaT. The keratinocytes were repeatedly irradiated with a visible light of wavelengths of 400-2000 nm (approximately 19,800 lux) in the presence or absence of Radical Sponge of 25-75 microM and did not exhibit any photo-cytotoxicity due to coexistent Radical Sponge as compared with the sham-irradiation control. Radical Sponge exerted a more marked cytoprotection at doses of 10-40 microM against UVA irradiation of 30 J/cm(2) when it was pre-irradiationally administered and rinsed out immediately before the irradiation, than when administered only during or after the irradiation, indicating the preventive rather than therapeutic or ray-sheltering effect of Radical Sponge on UVA injuries. Cytoprotection by Radical Sponge against UVA was achieved at the advisable range doses of 10-40 microM in contrast to no effect of polyvinylpyrrolidone alone; its dose-dependency was advantageous over that of VC-IP, a tetra-alkyl-esterized provitamin C, which became less cytoprotective above 20 microM. Thus, Radical Sponge is expected as an anti-UVA-preventive agent without visible-light-catalyzed cytotoxicity toward human skin keratinocytes.

Cytoprotection↗