Induced Cytotoxicity (induced + cytotoxicity)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Protective Effect of Ebselen on Aflatoxin B1 -Induced Cytotoxicity in Primary Rat Hepatocytes

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2000
Cheng-Feng Yang
Recent studies have shown that aflatoxin B1 enhances reactive oxygen species formation and causes oxidative damage, which may ultimately contribute to the cytotoxicity and carcinogenic effect of aflatoxin B1. Ebselen, 2-phenyl-1,2-benzoisoseleazol-3(H)-one, a synthetic seleno-organic compound has been shown to possess glutathione peroxidase-like activity and free radical scavenging ability. Thus present study was designed to investigate the protective effect of ebselen on aflatoxin B1 -induced cytotoxicity in primary rat hepatocytes. Aflatoxin B1 -induced cytotoxicity and lipid peroxidation were determined by lactate dehydrogenase leakage and malondialdehyde generation, respectively. Intracellular reactive oxygen species level was measured using the fluorescent probe 2,,7,-dichlorofluorescin diacetate, and the intracellular reduced glutathione concentration was determined with a fluorometric method. Ebselen was found to display a dose-dependent protective effect on lactate dehydrogenase leakage and malondialdehyde generation caused by aflatoxin B1 exposure. The results also demonstrate that ebselen efficiently inhibits the intracellular reactive oxygen species formation in aflatoxin B1 -treated hepatocytes in a dose and time-dependent manner. It was also noted that ebselen was able to increase the intracellular reduced glutathione concentration, both in the control and in aflatoxin B1 -treated hepatocytes. The protection of ebselen against aflatoxin B1 cytotoxicity, however, was not affected by lowering the concentration of intracellular reduced glutathione. The overall data indicate that ebselen possesses a potent protective effect against aflatoxin B1 -induced cytotoxicity, and the main mechanism involved in the protection may be its strong capability in inhibiting intracellular reactive oxygen species formation and preventing oxidative damage. [source]


The effect of focal adhesion kinase gene silencing on 5-fluorouracil chemosensitivity involves an Akt/NF-,B signaling pathway in colorectal carcinomas

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2010
Yuying Chen
Abstract Multicellular resistance (MCR) is produced because multicellular spheroids (MCSs) are formed with a broad cell,cell connection when cultured in three-dimensions, which limits the clinical treatment efficacy in solid tumors. Focal adhesion kinase (FAK) plays an important role in apoptosis, survival and cell adhesion between cells and their extracellular matrix. In this study, we investigated the expressions of FAK, Akt and NF-,B in human colorectal cancer (CRC), and the effects of FAK gene silencing on MCSs formation and 5-fluorouracil (5-FU) chemosensitivity in colon carcinoma MCSs culture cells. In CRC samples, FAK, Akt and NF-,B were overexpressed. The positive expression of FAK correlated notably with lymph node metastasis and cellular differentiation. Positive expressions of Akt and NF-,B were significantly related to cellular differentiation and lymph node metastasis, respectively. Furthermore, positive expression of FAK correlated with that of Akt and NF-,B. The expression of FAK was inhibited significantly by a small hairpin RNA targeting FAK. Knockdown of FAK reversed the formation and aggregation of MCSs, significantly decreased the 50% inhibitory concentration of 5-FU, and markedly increased MCS culture cells apoptosis. These effects were associated with reduced levels of Akt and NF-,B. These results indicate that suppressing FAK expression potentiated 5-FU-induced cytotoxicity and contributed to its chemosensitizing effect by suppressing Akt/NF-,B signaling in colon carcinoma MCS culture cells. These data also imply that FAK mediates MCR of CRC through the survival signaling pathway FAK/Akt/NF-,B. [source]


Bioefficacy and mode of action of rocaglamide from Aglaia elaeagnoidea (syn. A. roxburghiana) against gram pod borer, Helicoverpa armigera (Hbner)

JOURNAL OF APPLIED ENTOMOLOGY, Issue 3 2004
O. Koul
Abstract:, Rocaglamide, a highly substituted benzofuran, was isolated and identified as the main biologically active component in Aglaia elaeagnoidea (syn. A. roxburghiana) for gram pod borer Helicoverpa armigera (Hbner). Addition of rocaglamide to an artificial diet retarded the growth of neonate larvae in a dose-dependent manner with EC50 values of 0.76 p.p.m. These values compared favourably with azadirachtin (EC50 = 0.23 p.p.m.). However, azadirachtin was apparently more potent than rocaglamide in inducing growth inhibition via oral administration to these first stadium larvae. The candidate compound was found to have LD50 and LD95 values of 0.40 and 1.02 ,g per larva, respectively, in topical application against third instar larvae 96 h post-treatment. However, these values for azadirachtin were 8.16 and 25.8 ,g per larva for the same period. This shows that azadirachtin was less effective against third instar H. armigera larvae in inducing acute toxicity via topical treatment in comparison with rocaglamide. However, severe morphological larval deformities were observed in such azadirachtin-treated larvae during the process of ecdysis. The cytotoxic nature of rocaglamide was established by evaluating dietary utilization and the results did not implicate any antifeedant effect but the toxicity-mediated effect due to reduced efficiency of conversion of ingested food. It was obvious that feeding deterrence is not the primary mode of action but a centrally mediated effect, which could be due to the induced cytotoxicity at non-specific cellular levels. [source]


Methyl tert -butyl ether (MTBE)-induced cytotoxicity and oxidative stress in isolated rat spermatogenic cells

JOURNAL OF APPLIED TOXICOLOGY, Issue 1 2007
Dongmei Li
Abstract Methyl tert -butyl ether (MTBE) is a class of synthetic organic chemical. In the USA, MTBE pollution is regarded as a serious environmental problem. The objective of the present study was to investigate the cytotoxic effects and oxidative stress induced by MTBE in isolated rat spermatogenic cells. In cytotoxic experiments, spermatogenic cells isolated from the testes of adult Sprague-Dawley rats by a mechanical procedure without the use of trypsin were incubated with medium alone (control), 0.5, 5, 50 mm MTBE, respectively, for 6, 12 and 18 h. MTT assay, staining with fluorescein diacetate (FDA) and propidium iodide (PI) and flow cytometric analyses were used. In oxidative stress experiments, the spermatogenic cells were incubated with medium alone (control) and with 0.5, 50 ,m, 5 mm MTBE. For 1, 2, 6, 12, 18 h incubation, ROS production was tested using a 2,,7,-dichlorofluorescein diacetate (DCHF-DA) probe; for 1, 3, 6, 12, 18 h incubation, cytosolic superoxide dismutase (SOD) and extracellular SOD (SODEX) activity was assessed; and for 18 h incubation, lipid peroxidation was assessed. The results showed that MTBE at high doses significantly decreased the spermatogenic cell viability and increased plasma membrane damage and the ratio of necrotic cells compared with the control. Assessment of the MTBE-induced oxidative stress revealed that MTBE increased the production of reactive oxygen species (ROS) and enhanced lipid peroxidation. In addition, although SODEX activity increased at a high dose level, cytosolic SOD activity decreased. These results suggest that an increase of MTBE-induced ROS production and an enhancement of membrane lipid peroxidation may play an important role in its cytotoxicity in isolated rat spermatogenic cells. Copyright 2006 John Wiley & Sons, Ltd. [source]


PML/RAR, fusion protein mediates the unique sensitivity to arsenic cytotoxicity in acute promyelocytic leukemia cells: Mechanisms involve the impairment of cAMP signaling and the aberrant regulation of NADPH oxidase,

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008
Lingna Li
Acute promyelocytic leukemia (APL) cells are characterized by PML/RAR, fusion protein, high responsiveness to arsenic trioxide (ATO)-induced cytotoxicity and an abundant generation of reactive oxygen species (ROS). In this study we investigated the association among these three features in APL-derived NB4 cells. We found that NADPH oxidase-derived ROS generation was more abundant in NB4 cells compared with monocytic leukemia U937 cells. By using PR9, a sub-line of U937 stably transduced with the inducible PML/RAR, expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RAR, fusion protein, since PML/RAR,-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. On the other hand, the basal intensity of cAMP signaling pathway was compared between NB4 and U937 as well as between PR9 cells with or without PML/RAR,, demonstrating that PML/RAR,-expressing cells had an impaired cAMP signaling pathway which relieved its inhibitory effect on NADPH oxidase derived ROS generation. In summary, the present study demonstrated the correlation of PML/RAR, with cAMP signaling pathway, NADPH oxidase and ROS generation in APL cells. PML/RAR, that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO-induced cytotoxcity. J. Cell. Physiol. 217: 486,493, 2008. 2008 Wiley-Liss, Inc. [source]


Involvement of the nitric oxide/protein kinase G pathway in polychlorinated biphenyl-induced cell death in SH-SY 5Y neuroblastoma cells

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006
Lorella M.T. Canzoniero
Abstract Polychlorinated biphenyls (PCB) are persistent environmental contaminants whose chronic exposure can affect nervous system development and function. The cellular and molecular mechanisms underlying neuronal damage are not yet clear. In the present study, we investigated whether nitric oxide (NO) could be involved in aroclor 1254 (A1254; a PCB mixture)-induced cytotoxicity in SH-SY5Y human neuroblastoma cells. Prolonged exposure (24 hr) to A1254 (10,100 ,g/ml) caused a dose-dependent reduction of cell viability that was attenuated in the presence of a calcium entry blocker, gadolinum (Gd3+) at 10 ,M, a concentration able to block voltage-sensitive calcium channels. In addition, A1254 caused an increase of cytosolic calcium that was dependent on extracellular calcium, as measured by fura-2 videomicroscopy. A1254-induced calcium rise may stimulate NO production through an activation of neuronal NOS (nNOS). Indeed, the concomitant addition of the selective nNOS inhibitor N, -propyl- L -arginine (NPLA) and A1254 prevented cell injury, suggesting that NO production plays a major role in A1254-evoked cell injury. Furthermore, the exposure (14 hr) to A1254 (30 ,g/ml) produced an up-regulation of the expression of , isoform of nNOS. This up-regulation was calcium dependent and was accompanied by an enhancement of NO production as demonstrated by an increase of nitrite formation. Moreover, A1254-induced cell injury was prevented when KT 5823, a selective cGMP/PKG inhibitor, was added concomitantly to 30 ,g/ml A1254. These results suggest that PCB-induced cell death in neuroblastoma cells is mediated by an activation of the cGMP/PKG pathway triggered by NO production. 2006 Wiley-Liss, Inc. [source]


Heat shock proteins reduce toxicity of 1-methyl-4-phenylpyridinium ion in SK-N-SH cells

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005
Guo-Hua Fan
Abstract The pathology of Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, the pathogenesis of PD remains unclear. Heat shock proteins (HSPs) have many functions, including inhibition of apoptosis and necrosis, protection from oxidative stress, and maintenance of the mitochondrial membrane potential, that are related to neurodegenerative diseases. 1-Methyl-4-phenylpyridinium ion (MPP+) is a neurotoxin that selectively inhibits the mitochondrial functions of DA neurons in the substantia nigra. MPP+ administration is accepted as a model for PD. In the present study, we found that MPP+ induced a concentration- and time-dependent decrease in cell viability. Lower concentrations of MPP+ induced mainly early apoptosis, and, as the concentration increased, the number of late apoptotic and necrotic cells significantly increased. However, treated by heat shock preconditioning or transfection with HDJ-1, a homologue of human Hsp40, cells showed marked improvement in viability after exposure to the same concentrations of MPP+. Compared with heat shock, HDJ-1 appeared to improve cell viability obviously. Similarly, HDJ-1 elicited significantly stronger protective effects against apoptosis and necrosis. In addition, HDJ-1 transfection maintained more injured cells in early apoptotic stages and inhibited the occurrence of late apoptotic/necrotic events. Heat shock and HDJ-1 both ameliorated MPP+ -induced cytotoxicity by maintaining the mitochondrial membrane potential and reducing reactive oxygen species (ROS). Therefore, the effects of HSPs, such as reducing apoptosis and necrosis, preserving mitochondrial functions and decreasing oxidative stress, may bring a novel approach for PD therapy. 2005 Wiley-Liss, Inc. [source]


Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cells

MOLECULAR CARCINOGENESIS, Issue 4 2005
Yuko Yonezawa
Abstract Although the constitute activation of the Src family of kinases (Src) has been established as a poor prognostic factor in several types of cancer, the role of Src in renal cell carcinoma (RCC) has not been defined. This study aimed to determine whether Src could contribute to the appearance of malignant phenotypes in RCC. The role of Src in the appearance of malignant phenotypes in RCC was examined in two human renal cancer cell lines, Caki-1 from human metastatic RCC and ACHN from human primary RCC. Src activity in Caki-1 cells was higher than that in ACHN cells, and this difference corresponded to the difference of PP1 (a Src family inhibitor)-induced cytotoxicity on the two cells. The difference in cytotoxicity between the cells did not depend on cell cycle regulation but on the induction of apoptosis, and the difference in apoptosis particularly related to the reduction of the Bcl-xL level. Furthermore, in Caki-1 cells with higher Src activity, Src stimulated the production of vascular endothelial growth factor (VEGF), partially via the activation of Stat3, and the inhibition of Src activity caused a reduction of the VEGF level in serum, angiogenesis, and tumor development in a xenograft model. These results suggested that Src contributed to the appearance of malignant phenotypes in renal cancer cells, particularly due to the resistance against apoptosis by Bcl-xL and angiogenesis stimulated by Src-Stat3-VEGF signaling. 2005 Wiley-Liss, Inc. [source]


Neuroprotective effects of Triticum aestivum L. against ,-Amyloid-induced cell death and memory impairments

PHYTOTHERAPY RESEARCH, Issue 1 2010
Jung-Hee Jang
Abstract ,-Amyloid (A,) is a key component of senile plaques, neuropathological hallmarks of Alzheimer's disease (AD) and has been reported to induce cell death via oxidative stress. This study investigated the protective effects of Triticum aestivum L. (TAL) on A,-induced apoptosis in SH-SY5Y cells and cognitive dysfunctions in Sprague-Dawley (SD) rats. Cells treated with A, exhibited decreased viability and apoptotic features, such as DNA fragmentation, alterations in mitochondria and an increased Bax/Bcl-2 ratio, which were attenuated by TAL extract (TALE) pretreatment. To elucidate the neuroprotective mechanisms of TALE, the study examined A,-induced oxidative stress and cellular defense. TALE pretreatment suppressed A,-increased intracellular accumulation of reactive oxygen species (ROS) via up-regulation of glutathione, an essential endogenous antioxidant. To further verify the effect of TALE on memory impairments, A, or scopolamine was injected in SD rats and a water maze task conducted as a spatial memory test. A, or scopolamine treatment increased the time taken to find the platform during training trials, which was decreased by TALE pretreatment. Furthermore, one of the active components of TALE, total dietary fiber also effectively inhibited A,-induced cytotoxicity and scopolamine-caused memory deficits. These results suggest that TALE may have preventive and/or therapeutic potential in the management of AD. Copyright 2009 John Wiley & Sons, Ltd. [source]


The water extract of Omija protects H9c2 cardiomyoblast cells from hydrogen peroxide through prevention of mitochondrial dysfunction and activation of caspases pathway

PHYTOTHERAPY RESEARCH, Issue 1 2007
Channy Park
Abstract The water extract of Omija (Omija) has been used traditionally in the treatment of ischemic damage of the heart and brain tissues. However, little is known about the mechanism by which it rescues myocardial cells from oxidative stress. This study was designed to investigate the protective mechanisms of Omija on H2O2 -induced cytotoxicity in H9c2 cardiomyoblast cells. Treatment with H2O2 resulted in the death of H9c2 cells, characterized by apparent apoptotic features, including fragmentation of the nucleus and an increase in the sub-G0/G1 fraction of the cell cycle. However, Omija markedly suppressed the apoptotic characteristics of H9c2 cells induced by H2O2. In addition, Omija suppressed the features of mitochondrial dysfunction, including changes in the mitochondrial membrane potential and cytosolic release of cytochrome c in H2O2 -treated cells. Treatment with Omija further inhibited the catalytic activation of caspase-9 and caspase-3 and induction of Fas by H2O2. Taken together, these data indicate that the water extract of Omija protects H9c2 cardiomyoblast cells from oxidative stress of H2O2 through inhibition of mitochondrial dysfunction and activation of intrinsic caspase cascades, including caspase-3 and caspase-9. Copyright 2006 John Wiley & Sons, Ltd. [source]


Cysteine enhances clastogenic activity of dimethylarsinic acid

APPLIED ORGANOMETALLIC CHEMISTRY, Issue 7 2002
Mari Kitamura
Abstract The effects of cysteine on dimethylarsinic acid (DMA)-induced cytotoxicity and chromosomal aberration were studied using Chinese hamster V79 cells. The IC 50 of DMA, i.e. the concentration resulting in a 50% decrease in cell population of viable cells, was 130,g,ml,1 (0.94 mM), whereas that in the presence of 50,g,ml,1 (0.28 mM) cysteine was 20,g,ml,1 (0.14 mM). The mitotic index with co-administration of 50,g,ml,1 (0.36 mM) DMA and 50,g,ml,1 cysteine was 1.4 times that with 50,g,ml,1 DMA alone. Whereas 82% of cells divided twice with 25,g,ml,1 (0.18 mM) DMA alone, most cells divided only once with co-administration of 25,g,ml,1 DMA and 50,g,ml,1 cysteine. These results indicated that the increase in mitotic index by cysteine was due to enhancement of mitotic arrest by DMA. With co-administration of 25,g,ml,1 DMA and 50,g,ml,1 cysteine, tetraploidy was 14.3% higher and fivefold by that with 25,g,ml,1 DMA only. Cysteine at 50,g,ml,1 enhanced induction of chromosomal aberrant cells by DMA. 100,g,ml,1 (0.72 mM) DMA induced 91% chromosomal aberrant cells in the presence of cysteine, and 12% in the absence of cysteine. Chromatid breaks and chromatid gaps were the most frequent types of aberration induced by co-administration of DMA and cysteine or DMA alone. Co-administration of DMA and cysteine produced many attenuated chromosomal figures. The attenuated chromosomal figures always had several chromatid gaps and chromatid breaks. Our findings may provide clues to arsenic carcinogenesis in humans. Copyright 2002 John Wiley & Sons, Ltd. [source]


Effects on Lipid Peroxidation and Antioxidative Enzymes of Euonymus alatus in Cultured Rat Hepatocytes

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2009
Kyung-Woon Kim
In this paper, we investigate the effects of E. alatus on cultured hepatocyte cell system and lipid peroxidation in hydrogen peroxide (H2O2) treatment conditions. The study covers the physiological activity (the antioxidative activity and the nitrite-scavenging effect) of E. alatus. H2O2 that can produce intracellular free radical was used for inducer of the peroxidation of cellular lipids. Treatment of E. alatus attenuated in cell killing enhanced by increasing concentrations of H2O2. The increased malondialdehyde level induced by H2O2 treatment was reduced by pre-treatment of E. alatus. Furthermore, addition of E. alatus in cell culture medium significantly reduced cell killing and content of intracellular antioxidants. Changes in nitrite-scavenging effect of E. alatus at various concentrations (5,25 mg/ml) and various pH levels (pH 1.2, 4.2 and 6.0) were also observed. The present study was also done to investigate the effects of E. alatus on cultured hepatocyte cell system, H2O2 -induced cytotoxicity and antioxidative enzyme activities, including catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase in H2O2 treatment conditions. E. alatus treatment had significant protective or elevating activities on these antioxidative enzyme activities compared to a normal group. The results indicate that E. alatus provides a strong antioxidant protection of cells against H2O2 -induced oxidative stress. [source]


Protective Effect of Ebselen on Aflatoxin B1 -Induced Cytotoxicity in Primary Rat Hepatocytes

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2000
Cheng-Feng Yang
Recent studies have shown that aflatoxin B1 enhances reactive oxygen species formation and causes oxidative damage, which may ultimately contribute to the cytotoxicity and carcinogenic effect of aflatoxin B1. Ebselen, 2-phenyl-1,2-benzoisoseleazol-3(H)-one, a synthetic seleno-organic compound has been shown to possess glutathione peroxidase-like activity and free radical scavenging ability. Thus present study was designed to investigate the protective effect of ebselen on aflatoxin B1 -induced cytotoxicity in primary rat hepatocytes. Aflatoxin B1 -induced cytotoxicity and lipid peroxidation were determined by lactate dehydrogenase leakage and malondialdehyde generation, respectively. Intracellular reactive oxygen species level was measured using the fluorescent probe 2,,7,-dichlorofluorescin diacetate, and the intracellular reduced glutathione concentration was determined with a fluorometric method. Ebselen was found to display a dose-dependent protective effect on lactate dehydrogenase leakage and malondialdehyde generation caused by aflatoxin B1 exposure. The results also demonstrate that ebselen efficiently inhibits the intracellular reactive oxygen species formation in aflatoxin B1 -treated hepatocytes in a dose and time-dependent manner. It was also noted that ebselen was able to increase the intracellular reduced glutathione concentration, both in the control and in aflatoxin B1 -treated hepatocytes. The protection of ebselen against aflatoxin B1 cytotoxicity, however, was not affected by lowering the concentration of intracellular reduced glutathione. The overall data indicate that ebselen possesses a potent protective effect against aflatoxin B1 -induced cytotoxicity, and the main mechanism involved in the protection may be its strong capability in inhibiting intracellular reactive oxygen species formation and preventing oxidative damage. [source]


Neuroprotective effect of asymmetric dimethylarginine against 1-methyl-4-phenylpyridinium ion-induced damage in PC12 cells

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2010
Xiao-Qing Tang
Summary 1. Asymmetric dimethylarginine (ADMA) is a well-known endogenous nitric oxide synthase (NOS) inhibitor. Although it has been shown to be a novel risk marker in cardiovascular medicine and chronic kidney disease, we speculated that in some states associated with excess of nitric oxide (NO), such as 1-methyl-4-phenylpyridinium ion (MPP+)-induced neuronal injury, ADMA might be protective by limiting the toxic effect of high concentrations of NO. 2. The aim of the present study is to explore the protection of ADMA against MPP+ -induced apoptosis and the molecular mechanisms underlying in PC12 cells. 3. We found that exogenous application of ADMA obviously protected PC12 cells against MPP+ -induced cytotoxicity and apoptosis not only by reducing the loss of mitochondrial membrane potential, but also by attenuating an increase in intracellular reactive oxygen species. Moreover, ADMA attenuated MPP+ -induced excessive activation of nitric oxide synthase and overproduction of NO. 4. The results of the present study suggest that the protection caused by ADMA is related to preserving mitochondrial membrane potential and attenuating the MPP+ -induced intracellular reactive oxygen species generation through inhibiting nitric oxide synthase activity and limiting NO generation. [source]


EFFECT OF HYDROGEN SULPHIDE ON ,-AMYLOID-INDUCED DAMAGE IN PC12 CELLS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2008
Xiao-Qing Tang
SUMMARY 1Hydrogen sulphide (H2S) is a well-known cytotoxic gas. Recently, H2S has been shown to protect neurons against oxidative stress caused by glutamate, peroxynitrite and HOCl. Considerably lower H2S levels have been reported in the brain of Alzheimer's disease (AD) patients with accumulation of ,-amyloid (A,). 2The aim of present study was to explore the cytoprotection by H2S against A,25,35 -induced apoptosis and the molecular mechanisms underlying this effect in PC12 cells. 3Our findings indicated that A,25,35 significantly reduced cell viability and induced apoptosis of PC12 cells, along with dissipation of the mitochondrial membrane potential (MMP) and overproduction of reactive oxygen species (ROS). 4Sodium hydrosulphide (NaHS), an H2S donor, protected PC12 cells against A,25,35 -induced cytotoxicity and apoptosis not only by reducing the loss of MMP, but also by attenuating the increase in intracellular ROS. 5The results of the present study suggest that the cytoprotection by H2S is related to the preservation of MMP and attenuation of A,25,35 -induced intracellular ROS generation. These findings could significantly advance therapeutic approaches to the neurodegenerative diseases that are associated with oxidative stress, such as AD. [source]