Wyniki wyszukiwania

1

TNFalpha-induced activation of NFkappaB protects against UV-induced apoptosis specifically in p53-proficient cells

100%

Szoltysek K., Pietranek K., Kalinowska-Herok M., Pietrowska M., Kimmel M., Widlak P.

Acta Biochimica Polonica

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2008

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tom 55

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nr 4

741-748

The signaling pathways that depend on p53 or NFκB transcription factors are essential components of cellular responses to stress. In general, p53 is involved in either activation of cell cycle arrest or induction of apoptosis, while NFκB exerts mostly anti-apoptotic functions; both regulatory pathways apparently interfere with each other. Here we aimed to analyze the effects of NFκB activation on DNA damage-induced apoptosis, either p53-dependent or p53-independent, in a set of human cell lines. Four cell lines, HCT116 and RKO colon carcinoma, NCI-H1299 lung carcinoma and HL60 myeloblastoma, each of them in two congenic variants either containing or lacking transcriptionally competent p53, were used. Cells were incubated with TNFα cytokine to activate NFκB and then treated with ultraviolet or ionizing radiation to induce apoptosis, which was assessed by measurement of the sub-G1 cell fraction. We observed that treatment with TNFα resulted in a significant reduction in the frequency of apoptotic cells in UV-irradiated p53-proficient lines (with exception of the UV-resistant NCI-H1299 cells). This anti-apoptotic effect was lost when cells were pretreated with parthenolide, an inhibitor of NFκB activation. In marked contrast, TNFα-pretreatment of p53-deficient lines resulted in an increased frequency of apoptotic cells after UV irradiation (with exception of HL60 cells). Such anti- and pro-apoptotic influence of TNFα was less obvious in cells treated with ionizing radiation. The data clearly indicates functional interference of both signaling pathways upon the damage-induced apoptotic response, yet the observed effects are both cell type- and stimulus-specific.

2

Cytoprotective action of 17beta-oestradiol against iron-induced hepatic oxidative stress in vitro

100%

Wojcik M., Kosior-Korzecka U., Bobowiec R.

Bulletin of the Veterinary Institute in Puławy

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2010

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tom 54

|

nr 2

259-263

The objective of this study was to analyse the response of hepatocytes on various concentrations of 17ß-oestradiol (17ß-E) under iron-induced oxidative stress in vitro. Isolated by in situ collagenase perfusion hepatocytes were cultured in DMEM/HAMS-12 (v/v) medium without any additional agents (control), with Fe³⁺ alone, and with Fe³⁺ aild 0.2%, 0.02%, and 0.002% solution of 17ß-E (17ß-EI, 17ß-EII, and 17ß-EIII, respectively). After 24, 48, and 72 h, medium malonylodialdehyde (MDA), haptoglobin (Hpt) concentration and proliferative activity were determined. In comparison to control samples, and samples collected at 24 and 72 h, hepatocytes exposition to Fe³⁺, caused a significant increase in MDA (0.056 ±0.011 nM/mL) only after 48 h of incubation. Each of 17ß-E concentrations resulted in a decrease in MDA in samples obtained after 24 and 48 h. In comparison to the first 24 h, Fe³⁺ alone and together with 17ß-EI, 17ß-EII, and 17ß-EIII caused a significant augmentation of Hpt level in 48 h and 72 h of the experiment. Each of the 17ß-E concentrations added to the culture medium resulted in inhibition of hepatic proliferative activity, especially in the 72 h of cell culture.

3

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Role of leukotrienes and platelet activating factor in gastric mucosal damage and repair

100%

Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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1991

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tom 42

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nr 2

Gastric mucosal integrity depends upon the balance between „aggressive” factors and „defensive” mechanisms. The formation of mucosal lesions results from the disruption of defense lines, including the breaking of unstirred mucus layer, the reduction of surface hydrophobicity, extensive exfoliation of surface epithelium, penetration of offending agents deeply into the mucosa and damage to the microvessels. The release of proinflam- matory and vasoactive mediators such as leukotrienes (LT), thromboxanes, platelet activating factor (PAP), endothelins and others has been thought to be involved in the pathomechanism of mucosal injury, especially damage to the micro vascular endothelium, increased vascular permeability, reduction in mucosal blood flow, vascular stasis, tissue ischemia and glandular cell necrosis. This paper reviews the mechanisms and possible pathogenetic implication of two related compounds, LT and PAP in acute mucosal injury by topical irritants such as ethanol, aspirin, bile salts and by stress. LT and PAP arise from similar membrane phospholipids and may regulate the biosynthesis of one another in the damaged mucosa. Although pharmacological studies have clearly demonstrated the noxious effects of cysteinyl LT and PAP on the mucosa, especially when exposed to topical irritants, recent publications have challenged the primary role of these mediators in the pathogenesis of mucosal lesions and ulcerations because the treatment with agents that selectively antagonize their biosynthesis or the receptor sites at the target cells did not always interrupt the chain of events leading to mucosal injury. The role of these mediators in the mucosal repair processes has been little studied but both cysteinyl LT and PAP seem to delay the restitution and healing of the mucosa. Further studies are necessary to clarify to what extent the biosynthesis of LT and PAP and the pharmacological inhibition of their action on the target tissues is related to noxious, protective and reparative events in the mucosa exposed to mild irritants and ulcerogens.

4

Effects of sucralfate and its components on indomethacin-induced damage to cultured rabbit gastric mucosal cells

100%

Takahashi S., Okabe S.

Journal of Physiology and Pharmacology

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1996

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tom 47

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nr 4

5

Heme oxygenase-1 expression in disease states

100%

Deshane J., Wright M., Agarwal A.

Acta Biochimica Polonica

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2005

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tom 52

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nr 2

Heme oxygenase-1 (HO-1) is an enzyme which catalyzes the rate-limiting step in heme degradation resulting in the formation of iron, carbon monoxide and biliverdin, which is subsequently converted to bilirubin by biliverdin reductase. The biological effects exerted by the products of this enzymatic reaction have gained much attention. The anti-oxidant, anti-inflammatory and cytoprotective functions associated with HO-1 are attributable to one or more of its degradation products. Induction of HO-1 occurs as an adaptive and beneficial response to several injurious stimuli including heme and this inducible nature of HO-1 signifies its importance in several pathophysiological disease states. The beneficial role of HO-1 has been implicated in several clinically relevant disease states involving multiple organ systems as well as significant biological processes such as ischemia-reperfusion injury, inflammation/immune dysfunction and transplantation. HO-1 has thus emerged as a key target molecule with therapeutic implications.

6

New aspects of clinical pharmacology of antacids

100%

Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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1993

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tom 44

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nr 1

7

Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4

84%

Pietruczuk K., Jozwik A., Ruckemann-Dziurdzinska K., Bryl E., Witkowski J. M.

Folia Histochemica et Cytobiologica

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2009

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tom 47

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nr 4

8

Comparison of prostaglandin and cimetidine in protection of isolated gastric glands against indomethacin injury

84%

Brzozowski T., Tarnawski A., Hollander D., Sekhon S., Krause W. J., Gergely H.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 5

75-88

Prostaglandins can protect the in vivo gastric mucosa against necrosis produced by a variety noxious agents. Cimetidine has also been shown to have protective properties in humans and in some models of experimental injury. Whether prostaglandins or cimetidine may protect gastric mucosal cells directly in the absence of systemic factors remains controversial. In the present study, the potential protective actions of prostaglandin and cimetidine against indomethacin injury were assessed in isolated rat gastric glands. Gastric glands were pre-incubated in oxygenated medium with either placebo, 16,16 dimethyl prostaglandin E2 (dm PGE2) or cimetidine and incubated at 37°C in medium containing 0.5 mg/ml of indomethacin for 2, 4 and 6 hrs. Cell injury and protection was assessed by the Fast Green exclusion test (viability test), leakage of lactate dehydrogenase (LDH) into the medium, and by scanning and transmission electron microscopy. In addition, the generation of PGE2 by the gland cells was determined using RIA assay. Indomethacin by itself significantly reduced the viability of gastric glands, increased LDH release into the medium and produced prominent ultrastructural damage. In contrast to cimetidine, co-incubation of gastric glands with dm PGE2 added to indomethacin, significantly reduced indomethacin-induced injury, increased the number of viable cells, reduced LDH leakage and diminished the extent of ultrastructural damage. The dose of indomethacin (5 µg/ml) which significantly inhibited the generation of PGE2 (up to 90% inhibition) had no effect on cell viability nor LDH release. We conclude that 1) exogenous PGE2 exerts a potent protective activity in vitro which is independent on neural, vascular and hormonal factors; 2) inhibition of endogenous PGs may not the primary mechanism in the deleterious action of indomethacin against damage to gastric glandular cells and 3) indomethacin can exert a direct cytotoxic effect on the mucosal cells in gastric glands.

9

An endogenous defensive concept, renewed cytoprotection/adaptive cytoprotection: intra(per)-oral/intragastric administration of strong alcohol in rat. Involvement of pentadecapeptide BPC 157 and nitric oxide system

84%

Becejac T., Cesarec V., Drmic D., Hirsl D., Madzarac G., Djakovic Z., Bunjevac I., Zenko Sever A., Sepac A., Batelja Vuletic L., Stancic Rokotov D., Seiwerth S., Sikiric P.

Journal of Physiology and Pharmacology

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2018

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tom 69

|

nr 3

10

Endothelium as target for large-conductance calcium-activated potassium channel openers

84%

Wrzosek A.

Acta Biochimica Polonica

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2009

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tom 56

|

nr 3

393-404

The endothelium is a highly active organ responsible for vasculatory tone and structure, angiogenesis, as well as hemodynamic, humoral, and inflammatory responses. The endothelium is constantly exposed to blood flow, sheer stress and tension. Endothelial cells are present as a vasculature in every tissue of the body and react to and control its microenvironment. A variety of ion channels are present in the plasma membranes of endothelial cells. These include potassium channels such as inwardly rectifying potassium (Kir) channels, voltage-dependent (Kv) channels, ATP-regulated potassium (KATP) channels and three types of calcium-activated potassium channels (KCa), the large (BKCa), intermediate (IKCa), and small (SKCa) -conductance potassium channels. Potassium current plays a critical role in action potentials in excitable cells, in setting the resting membrane potential, and in regulating neurotransmitter release. Mitochondrial isoforms of potassium channel contribute to the cytoprotection of endothelial cells. Prominent among potassium channels are families of calcium-activated potassium channels, and especially large-conductance calcium-activated potassium channels. The modulation of BKCa channels, which are voltage- and calcium-dependent, has been intensively studied. The BKCa channels show large expression dynamics in endothelial cells and tissue-specific expression of large numbers of alternatively spliced isoforms. In this review, a few examples of the modulatory mechanisms and physiological consequences of the expression of BKCa channels are discussed in relation to potential targets for pharmacological intervention.

11

Effects of ethanol and arachidonic acid pathway inhibitors on the effectiveness of gastric mucosa cytoprotection

84%

Lutnicki K., Szpringer E., Czerny K., Ledwozyw A.

Folia Morphologica

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2001

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tom 60

|

nr 1

Cytoprotection in the stomach, consisting in the mucus secretion, mucous circulation intensification and bicarbonate secretion to the gastric lumen, is highly dependent on the products of arachidonic acid pathway and peroxidative-antioxidative balance. The aim of the paper was to examine the effects of selected inhibitors of arachidonic acid pathway on the natural protective system of the gastric mucosa exposed to 50% ethanol. The results show that leukotrienes, thromboxane and oxygen reactive forms significantly impair the protective function of the gastric mucosa while prostaglandins and antioxidant enzymes act protectively.

12

Studies on gastroprotection induced by capsaicin and papaverine

84%

Brzozowski T., Drozdowicz D., Majka J., Konturek S. J.

Journal of Physiology and Pharmacology

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1992

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tom 43

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nr 4

Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) but the possibility that NO mediates the protective and hyperemic effects of capsaicin and papaverine has been little studied. Using N-nitro-L-arginine (L-NNA), a selective blocker of NO synthase, and L-arginine as a substrate for NO, we investigated the role of NO in protective action of capsaicin and papaverine against ethanol-induced gastric damage and in GBF. Pretreatment with capsaicin (0.1-0.5mg/kg i. g.) or papaverine (0.1-2mg/kg i.g.) reduced dose-dependently the area of ethanol- induced lesions, the LD50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous (i. v.) injection of L-NNA (1.2-5 mg/kg), which by itself caused only a small increase in ethanol lesions, reversed dose-dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i. v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhaced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L-NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.

13

Ischemic preconditioning attenuates gastric ischemia-reperfusion injury through involvement of glucocorticoids

67%

Bobryshev P., Bagaeva T., Filaretova L.

Journal of Physiology and Pharmacology. Supplement

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2009

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tom 60

|

nr 7

14

Gastroprotective effects of flavonoids in plant extracts

67%

Zayachkivska O. S., Konturek S. J., Drozdowicz D., Konturek P. C., Brzozowski T., Ghegotsky M. R.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

|

nr 1

219-231

The purpose of this paper is to overview the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulcer activities. In addition, we assessed whether these compounds are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically (i.g.). The following plant-originated flavonoid substances were considered; Solon (Sophoradin extract), Amaranth seed extract, grapefruit-seed extract (GSE) and capsaicin (extract of chilly pepper). The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). Male Wistar rats, weighing 180-220 g fasted for 24 h before the study where used 100% ethanol was applied i.g. to induce gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment with L-NNA. We conclude that plant-originated flavonoid substances are highly gastroprotective probably due to enhancement of the expression of constitutive NOS and release of NO and neuropeptides such as calcitonin gene related peptide (CGRP) released from sensory afferent nerves increasing gastric microcirculation.

15

Dietary threonine prevented stress-related mucosal diseases in rats

67%

An J. M., Kang E. A., Han Y. M., Kim Y. S., Hong Y. G., Hah B. S., Hong S. P., Hahm K. B.

Journal of Physiology and Pharmacology

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2019

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tom 70

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nr 3

16

Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy

67%

Hrelec M., Klicek R., Brcic L., Brcic I., Cvjetko I., Seiwerth S., Sikiric P.

Journal of Physiology and Pharmacology. Supplement

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2009

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tom 60

|

nr 7

17

Prostaglandins and brain-gut axis

67%

Dajani E. Z., Shahwan T. G., Dajani N. E.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

|

nr 4

155-164

Prostaglandins (PGs) have well documented physiological and pharmacological actions on the gastrointestinal (GI) tract. This communication reviews the evidence for peripheral and central nervous system (CNS) physiological actions of PGs in order to determine their role in the brain-gut axis, if any. PGs are widely distributed in nearly all cells peripherally and centrally. Laboratory and clinical evidence indicate that there is a direct relationship between altered GI physiological functions and peripheral PGs biosynthesis. Either local or parenteral administration of natural E-series PGs alters GI physiological functions particularly those relating to mucosal defense. Furthermore, the cyclooxygenase enzymes (COX), which are responsible for the PGs biosynthesis, have been localized in the brain as well as peripherally. However, increased levels of PGs in the brain have been associated with pathological processes such as inflammation, pain, fever and addiction. Although PGs have been shown to modulate CNS effects of catecholaminergic, serotoninergic and cholinergic neurons, there is no meaningful information concerning their direct central effect on GI function. The evidence for a clear physiological role of central PGs on the GI tract is not convincing. At this time, we conclude that PGs primarily manifest their activity on the GI tract by peripheral rather than by central mechanisms.

18

Hydrogen sulfide-induced colonic mucosal cytoprotection involves T-type calcium channel-dependent neuronal excitation in rats

67%

Matsunami M., Kirishi S., Okui T., Kawabata A.

Journal of Physiology and Pharmacology

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2012

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tom 63

|

nr 1

19

Different effects of simvastatin on ex vivo monocyte cytokine release in patients with hypercholesterolemia and impaired glucose tolerance

67%

Krysiak R., Okopien B.

Journal of Physiology and Pharmacology

|

2010

|

tom 61

|

nr 6

20

Exploring the potential of Crotalaria juncea flower extracts as a source of antioxidants, antimicrobials, and cytoprotective agents for biomedical applications

67%

Mahasawat P., Boukaew S., Prasertsan P.

BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology

|

2023

|

tom 104

|

nr 4

Ograniczanie wyników

TNFalpha-induced activation of NFkappaB protects against UV-induced apoptosis specifically in p53-proficient cells

Cytoprotective action of 17beta-oestradiol against iron-induced hepatic oxidative stress in vitro

Role of leukotrienes and platelet activating factor in gastric mucosal damage and repair

Effects of sucralfate and its components on indomethacin-induced damage to cultured rabbit gastric mucosal cells

Heme oxygenase-1 expression in disease states

New aspects of clinical pharmacology of antacids

Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4

Comparison of prostaglandin and cimetidine in protection of isolated gastric glands against indomethacin injury

An endogenous defensive concept, renewed cytoprotection/adaptive cytoprotection: intra(per)-oral/intragastric administration of strong alcohol in rat. Involvement of pentadecapeptide BPC 157 and nitric oxide system

Endothelium as target for large-conductance calcium-activated potassium channel openers

Effects of ethanol and arachidonic acid pathway inhibitors on the effectiveness of gastric mucosa cytoprotection

Studies on gastroprotection induced by capsaicin and papaverine

Ischemic preconditioning attenuates gastric ischemia-reperfusion injury through involvement of glucocorticoids

Gastroprotective effects of flavonoids in plant extracts

Dietary threonine prevented stress-related mucosal diseases in rats

Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy

Prostaglandins and brain-gut axis

Hydrogen sulfide-induced colonic mucosal cytoprotection involves T-type calcium channel-dependent neuronal excitation in rats

Different effects of simvastatin on ex vivo monocyte cytokine release in patients with hypercholesterolemia and impaired glucose tolerance

Exploring the potential of Crotalaria juncea flower extracts as a source of antioxidants, antimicrobials, and cytoprotective agents for biomedical applications