Attenuation of Rotenone-Induced Mitochondrial Oxidative Damage and Neurotoxicty in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> Supplemented with Creatine

Creatine (Cr), an ergogenic nutritional supplement is demonstrated to possess bioenergetic, antiexcitotoxic and antioxidant properties. This study investigated the neuroprotective effects of Cr against rotenone induced oxidative stress, mortality and neurotoxicty in Drosophila melanogaster. We found significant diminution in the endogenous levels of oxidative markers in whole body homogenates of flies exposed to Cr (2–10 mM). Cr supplementation resulted in reduced mortality in flies exposed to rotenone (500 μM) and better performance in a negative geotaxis assay. Further Cr (10 mM) markedly offset rotenone induced mitochondrial oxidative stress, completely restored the GSH levels, nitric oxide levels, activity of Mn-SOD and dopamine depletion. In an oxidative stress bioassay, flies given Cr prophylaxis exhibited marked resistance to paraquat exposure. These data allow us to hypothesize that the neuroprotective action of Cr in Drosophila may be related to its direct antioxidant activity and ability to abrogate rotenone induced mitochondrial oxidative stress.     

Modulating effects of hesperidin on circadian pattern indices of rotenone induced redox homeostasis in clock mutant (cryb) of Drosophila melanogaster

The circadian timing system controls drug metabolism and cellular processes over the 24 h period in every cell. Impaired redox homeostasis is a casual factor for a number of diseases and it is desirable to understand the orchestration of circadian clock under oxidative stress in the model organism, Drosophila melanogaster. This study evaluates the effect of hesperidin on the circadian rhythms of lipid peroxidation products and antioxidants during rotenone-induced oxidative stress in fruit fly. The characteristics of temporal rhythms (acrophase, amplitude, and mesor) of glutathione peroxides (GPx), reduced glutathione (GSH)), were markedly declined in rotenone-treated flies when compared to other groups. Treatment of hesperidin to rotenone-treated flies significantly increased the mesor and modified the amplitudes of antioxidants. Further, delays in acrophase in rotenone-induced flies were reversed by hesperidin treatment. Thus, treatment of hesperidin results in normalization of the altered rhythms of these indices plausibly by its cytoprotective and antioxidant effects. Impairment of 24 h rhythms in oxidative stress markers and antioxidants were observed during rotenone treatment and the impairment is severe in circadian clock mutant cry^b flies. A reversibility of rhythms was prominent consequent to hesperidin treatment in wild-type flies than cry^b flies. These findings revealed a role of circadian clock in redox homeostasis and the use of Drosophila model in screening putative antioxidative phytomedicines earlier to their use in mammalian systems.     

Diphenyl Diselenide Protects Against Mortality,Locomotor Deficits and Oxidative Stress in Drosophila melanogaster Model of Manganese-Induced Neurotoxicity

Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 µmol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese-induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure.

     

Ceruloplasmin Protects Against Rotenone-Induced Oxidative Stress and Neurotoxicity

To clarify the neuroprotective property of ceruloplasmin and the pathogenesis of aceruloplasminemia, we generated ceruloplasmin-deficient (CP ^−/−) mice on the C57BL/10 genetic background and further treated them with a mitochondrial complex I inhibitor, rotenone. There was no iron accumulation in the brains of CP ^−/− mice at least up to 60 weeks of age. Without rotenone treatment, CP ^−/− mice showed slight motor dysfunction compared with CP ^+/+ mice, but there were no detectable differences in the levels of oxidative stress markers between these two groups. A low dose of rotenone did not affect the mitochondrial complex I activity in our mice, however, it caused a significant change in motor behavior, neuropathology, or the levels of oxidative stress markers in CP ^−/− mice, but not in CP ^+/+ mice. Our data support that ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity, probably through its antioxidant properties independently of its function of iron metabolism.     

Effect of hesperidin on the temporal regulation of redox homeostasis in clock mutant (Cryb) of Drosophila melanogaster

Disorganized redox homeostasis is a main factor causing a number of diseases and it is imperative to comprehend the orchestration of circadian clock under oxidative stress in the organism, Drosophila melanogaster. This investigation analyses the influence of hesperidin on the circadian rhythms of lipid peroxidation products and antioxidants during rotenone-stimulated oxidative stress in fruit fly. The characteristics of rhythms of thiobarbituric acid reactive substances (TBARS), antioxidants (superoxide dismutase (SOD) and catalase (CAT)) were noticeably decreased in rotenone administered flies. Supplementation of hesperidin to rotenone-treated flies increased the mesor and modulated the amplitudes of antioxidants and conspicuously decreased the mesor values of TBARS. In addition, delays in acrophase in rotenone-induced flies were reversed by hesperidin treatment. Thus, treatment of hesperidin caused normalization of the altered rhythms. Disorganization of 24 h rhythms in markers of redox homeostasis was observed during rotenone treatment and the impairment is severe in circadian clock mutant (Cryb) flies. Reversibility of rhythms was prominent subsequent to hesperidin treatment in wild-type flies than (Cryb) flies. These observations denote a role of circadian clock in redox homeostasis and the use of Drosophila model in screening putative antioxidative phytomedicines prior to their usage in mammalian systems.     

Detoxified Extract of <Emphasis Type="Italic">Rhus verniciflua</Emphasis> Stokes Inhibits Rotenone-Induced Apoptosis in Human Dopaminergic Cells,SH-SY5Y

Rhus verniciflua Stokes (RVS), traditionally used as a food supplement and in traditional herbal medicine for centuries in Korea, is known to possess various pharmacological properties. Environmental neurotoxins such as rotenone, a specific inhibitor of complex I provide models of Parkinson’s disease (PD) both in vivo and in vitro. In this study, we investigated the neuroprotective effect of RVS against rotenone-induced toxicity in human dopaminergic cells, SH-SY5Y. Cells exposed to rotenone for 24 h-induced cellular injury and apoptotic cell death. Pretreatment of cells with RVS provided significant protection to SH-SY5Y cells. Further, RVS offered remarkable protection against rotenone-induced oxidative stress and markedly inhibited mitochondrial membrane potential (MMP) disruption. RVS also attenuated the up-regulation of Bax, Caspase-9 and Caspase-3 and down-regulation of Bcl-2. Moreover, pretreatment with RVS prevented the decrease in tyrosine hydroxylase (TH) levels in SH-SY5Y cells. Interestingly, RVS conferred profound protection to human dopaminergic cells by preventing the downregulation of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). These results suggest that RVS may protect dopaminergic neurons against rotenone-induced apoptosis by multiple functions and contribute to neuroprotection in neurodegenerative diseases, such as PD.     

PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone

In vivo and in vitro studies have suggested a neuroprotective role for Pituitary adenylate cyclase activating polypeptide (PACAP) against neuronal insults. Here, we showed that PACAP27 protects against neurotoxicity induced by rotenone, a mitochondrial complex I inhibitor that has been implicated in the pathogenesis of Parkinson's disease (PD). The neuroprotective effect of PACAP27 was dose-dependent and blocked by its specific receptor antagonist, PACAP6-27. The effects of PACAP27 on rotenone-induced cell death were mimicked by dibutyryl-cAMP (db-cAMP), forskolin and prevented by the PKA inhibitor H89, the ERK inhibitor PD98059 and the p38 inhibitor SB203580. PACAP27 administration blocked rotenone-induced increases in the level of caspase-3-like activity, whereas could not restore mitochondrial activity damaged by rotenone. Thus, our results demonstrate that PACAP27 has a neuroprotective role against rotenone-induced neurotoxicity in neuronal differentiated PC12 cells and the neuroprotective effects of PACAP are associated with activation of MAP kinase pathways by PKA and with inhibition of caspase-3 activity; the signaling mechanism appears to be mediated through mitochondrial-independent pathways.     

Dual effects of α-synuclein on neurotoxicity induced by low dosage of rotenone are dependent on exposure time in dopaminergic neuroblastoma cells

This study was designed to investigate the effects of α-synuclein on toxicity induced by long-term exposure to relatively low concentrations of rotenone.Compared with the control groups,the inhibition of cell viability which overexpressed α-synuclein(SH-SY5Y-Syn) improved after 1 and 2 weeks of rotenone treatment.The complex I activity was greater and the mitochondrial membrane swelling intensity was reduced after 1 and 2 weeks of treatment,which indicated that α-synuclein,at least in part,resists the rotenone-induced oxidative stress.The results indicate that α-synuclein has a dual effect on toxicity of rotenone according to exposure time in human SH-SY5Y cells.     

Mangiferin Antagonizes Rotenone: Induced Apoptosis Through Attenuating Mitochondrial Dysfunction and Oxidative Stress in SK-N-SH Neuroblastoma Cells

In the present study, using a human neuroblastoma SK-N-SH cells, we explored antioxidant, mitochondrial protective and antiapoptotic properties of mangiferin against rotenone-mediated cytotoxicity. SK-N-SH cells are divided into four experimental groups based on 3-(4,5-dimethyl2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay—untreated cells, cells incubated with rotenone (100 nM), cells treated with mangiferin (20 μg) (pretreatment 4 h before) + rotenone (100 nM) and mangiferin alone treated. 24 h after treatment with rotenone and 28 h after treatment with mangiferin, levels of ATP thiobarbituricacid reactive substances and reduced glutathione and activities of enzymatic antioxidants including superoxide dismutase, catalase and glutathione peroxidise were measured. Finally mitochondrial transmembrane potential and expressions of apoptotic protein were also analysed. Pre-treatment with mangiferin significantly enhanced cell viability, ameliorated decrease in mitochondrial membrane potential and decreased rotenone-induced apoptosis in the cellular model of Parkinson’s disease. Moreover oxidative imbalance induced by rotenone was partially rectified by mangiferin. Our results indicated that anti-apoptotic properties of this natural compound due to its antioxidant and mitochondrial protective function protect rotenone induced cytotoxicity.     

Dietary consumption of monosodium L‐glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster

Adaptive response is the ability of an organism to better counterattack stress‐induced damage in response to a number of different cytotoxic agents. Monosodium L‐glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5‐g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H₂O₂), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S‐transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H₂O₂ generations and total thiol content as well as the activities of catalase and glutathione S‐transferase in D. melanogaster (P < .05). In conclusion, consumption of MSG for 5 days by D. melanogaster induced adaptive response, but long‐term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors.     

Platelet-rich plasma ameliorates neurotoxicity induced by silver nanoparticles in male rats via modulation of apoptosis,inflammation, and oxidative stress

The widespread use of silver in various forms raises concerns about its potential adverse effects. Silver nanoparticles (AgNPs) can enter the brain and subsequently induce neurotoxicity. As a source of diverse growth factors and for its cytoprotective properties, platelet-rich plasma (PRP) has received considerable attention in regenerative medicine. Our aim was to estimate the toxic effects of AgNPs on the rat brain and assess the possible protective effects of PRP against AgNPs induced neurotoxicity. A total of 40 adult male rats were divided into four groups (n = 10), namely the control, AgNPs, AgNPs+PRP, and auto-recovery groups. AgNPs were given intraperitoneally (i.p.) at a 10 mg/kg dose.bw daily for 28 days. PRP was given (a day after AgNPs treatment) i.p. at a dose of 0.5 mL/kg.bw twice weekly for 3 weeks. Rats in the auto-recovery group were left without treatment for 3 weeks after AgNP toxicity. Serum and brain tissue samples were collected for assessment of proinflammatory cytokines, oxidative stress markers, as well as the expression levels of apoptotic markers. Brain histopathological and immunohistochemistry examinations were done. AgNPs significantly increased oxidative stress markers and proinflammatory cytokines, decreased antioxidant defense markers, and induced apoptosis and histopathological brain injuries. However, PRP treatment restored brain oxidant/antioxidant balance, attenuated the inflammatory state, prevented apoptosis, and improved the brain histopathological lesions induced by AgNPs, with no significant improvements shown by auto-recovery group. Our data provided a novel protective effect for PRP against AgNPs-induced neurotoxicity due to its antioxidant, anti-inflammatory, and antiapoptotic effects.     

Betaine Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells

Rotenone is an inhibitor of mitochondrial complex I-induced neurotoxicity in PC12 cells and has been widely studied to elucidate the pathogenesis of Parkinson’s disease. We investigated the neuroprotective effects of betaine on rotenone-induced neurotoxicity in PC12 cells. Betaine inhibited rotenone-induced apoptosis in a dose-dependent manner, with cell viability increasing from 50 % with rotenone treatment alone to 71 % with rotenone plus 100-μM betaine treatment. Flow cytometric analysis demonstrated cell death in the rotenone-treated cells to be over 50 %; the number of live cells increased with betaine pretreatment. Betaine pretreatment of PC12 cells attenuated rotenone-mediated mitochondrial dysfunction, including nuclear fragmentation, ATP depletion, mitochondrial membrane depolarization, caspase-3/7 activation, and reactive oxygen species production. Western blots demonstrated activation of caspase-3 and caspase-9, and their increased expression levels in rotenone-treated cells; betaine decreased caspase-3 and caspase-9 expression levels and suppressed their activation. Together, these results suggest that betaine may serve as a neuroprotective agent in the treatment of neurodegenerative diseases.     

Hesperidin ameliorates heavy metal induced toxicity mediated by oxidative stress in brain of Wistar rats

Cadmium (Cd) induces neurotoxicity owing to its highly deleterious capacity to cross the blood brain barrier (BBB). Recent studies have provided insights on antioxidant properties of bioflavonoids which have emerged as potential therapeutic and nutraceutical agents. The aim of our study was to examine the hypothesis that hesperidin (HP) ameliorates oxidative stress and may have mitigatory effects in the extent of heavy metal-induced neurotoxicity. Cd (3 mg/kg body weight) was administered subcutaneously for 21 days while HP (40 mg/kg body weight) was administered orally once every day. The results of the current investigation demonstrate significant elevated levels of oxidative stress markers such as lipid peroxidation (LPO) and protein carbonyl (PC) along with significant depletion in the activity of non-enzymatic antioxidants like glutathione (GSH) and non-protein thiol (NP-SH) and enzymatic antioxidants in the Cd treated rats’ brain. Activity of neurotoxicity biomarkers such as acetylcholinesterase (AchE), monoamine oxidase (MAO) and total ATPase were also altered significantly and HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers while salvaging the antioxidant sentinels of cells to near normal levels thus exhibiting potent antioxidant and neuroprotective effects on the brain tissue against oxidative damage in Cd treated rodent model.     

Rutin from Dendropanax morbifera Leveille Protects Human Dopaminergic Cells Against Rotenone Induced Cell Injury Through Inhibiting JNK and p38 MAPK Signaling

Dendropanax morbifera Leveille (Araliaceae) is well known in Korean traditional medicine for a variety of diseases. Rotenone is a commonly used neurotoxin to produce in vivo and in vitro Parkinson’s disease models. This study was designed to elucidate the processes underlying neuroprotection of rutin, a bioflavonoid isolated from D. morbifera Leveille in cellular models of rotenone-induced toxicity. We found that rutin significantly decreased rotenone-induced generation of reactive oxygen species levels in SH-SY5Y cells. Rutin protected the increased level of intracellular Ca²⁺ and depleted level of mitochondrial membrane potential (ΔΨm) induced by rotenone. Furthermore, it prevented the decreased ratio of Bax/Bcl-2 caused by rotenone treatment. Additionally, rutin protected SH-SY5Y cells from rotenone-induced caspase-9 and caspase-3 activation and apoptotic cell death. We also observed that rutin repressed rotenone-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation. These results suggest that rutin may have therapeutic potential for the treatment of neurodegenerative diseases associated with oxidative stress.     

Hesperidin modulates the rhythmic proteomic profiling in Drosophila melanogaster under oxidative stress

The circadian clock regulates vital aspects of physiology including protein synthesis and oxidative stress response. In this investigation, we performed a proteome-wide scrutiny of rhythmic protein accrual in Drosophila melanogaster on exposure to rotenone, rotenone + hesperidin and hesperidin in D. melanogaster. Total protein from fly samples collected at 6 h intervals over the 24 h period was subjected to two-dimensional gel electrophoresis and mass spectrometry. Bioinformatics tool, Protein ANalysis THrough Evolutionary Relationships classification system was used to the determine the biological processes of the proteins of altered abundance. Conspicuous variations in the proteome (151 proteins) of the flies exposed to oxidative stress (by rotenone treatment) and after alleviating oxidative stress (by hesperidin treatment) were observed during the 24 h cycle. Significantly altered levels of abundance of a wide variety of proteins under oxidative stress (rotenone treatment) and under alleviation of oxidative stress (rotenone + hesperidin treatment) and hesperidin (alone) treatment were observed. These proteins are involved in metabolism, muscle activity, heat shock response, redox homeostasis, protein synthesis/folding/degradation, development, ion-channel/cellular transport, and gustatory and olfactory function of the flies. Our data indicates that numerous cellular processes are involved in the temporal regulation of proteins and widespread modulations happen under rotenone treatment and, action of hesperidin could also be seen on these categories of proteins.     

Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson's disease

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD). The important biochemical features of PD, being profound deficit in dopamine (DA) content, reduced glutathione (GSH), and enhanced lipid peroxidation (LPO) in dopaminergic (DA-ergic) neurons resulting in oxidative stress, mitochondrial dysfunction and apoptosis. Rotenone-induced neurotoxicity is a well acknowledged preclinical model for studying PD in rodents as it produces selective DA-ergic neuronal degeneration. In our previous study, we have shown that chronic administration of rotenone to rats is able to produce motor dysfunction, which increases progressively with rotenone treatment and centrophenoxine (CPH) co-treatment is able to attenuate these motor defects. The present study was carried out to evaluate the antioxidant potential of CPH against rotenone-induced oxidative stress. Chronic administration of rotenone to SD rats resulted in marked oxidative damage in the midbrain region compared to other regions of the brain and CPH co-treatment successfully attenuated most of these changes. CPH significantly attenuated rotenone-induced depletion in DA, GSH and increase in LPO levels. In addition, the drug prevented the increase in nitric oxide (NO) and citrulline levels and also enhanced the activity of catalase and superoxide dismutase (SOD). Histological analysis carried out using hematoxylin and eosin staining has indicated severe damage to mid brain in comparison to cortex and cerebellum and this damage is attenuated by CPH co-treatment. Our results strongly indicate the possible therapeutic potential of centrophenoxine as an antioxidant in Parkinson's disease and other movement disorders where oxidative stress is a key player in the disease process.     

Synergistic protective effect of paeoniflorin and β-ecdysterone against rotenone-induced neurotoxicity in PC12 cells

There are several factors, like oxidative stress and neurons loss, involving neurodegenerative diseases such as Parkinson’s disease (PD). The combination of antioxidant and anti-apoptotic agent is becoming a promising approach to fight against PD. This study evaluates the hypothesis that paeoniflorin (PF) and β-ecdysterone (β-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin rotenone. The combination of PF and β-Ecd, hereafter referred to as the PF/β-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner. PF and β-Ecd cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax expression, caspase-9 activity, and caspase-3 activity. PF or PF/β-Ecd, but not β-Ecd, inhibited rotenone-triggered protein kinase C-δkinase C-δ (PKCδ) upregulation and nuclear factor κB (NF-κB) activation. β-Ecd or PF/β-Ecd, but not PF, enhanced serine/threonine protein kinase (Akt) activation, promoted nuclear factor E2-related factor 2 (Nrf2) nuclear accumulation, suppressed reactive oxygen species (ROS) production. Neuroprotection of PF/β-Ecd could be completely blocked by PKCδ inhibitor rottlerin plus Akt specific inhibitor LY294002. Dual blockade of the PKCδ/NF-κB pathway by PF and activation of Akt/Nrf2 pathway by β-Ecd results in a synergistic neuroprotective effect against rotenone-induced neurotoxicity in vitro. These findings provide the rationale for determining the in vivo activity of combined therapy with PF and β-Ecd against PD.     

Aminoethoxydiphenyl Borate and Flufenamic Acid Inhibit Ca<Superscript>2+</Superscript> Influx Through TRPM2 Channels in Rat Dorsal Root Ganglion Neurons Activated by ADP-Ribose and Rotenone

Exposure to oxidative stress causes health problems, including sensory neuron neuropathy and pain. Rotenone is a toxin used to generate intracellular oxidative stress in neurons. However, the mechanism of toxicity in dorsal root ganglion (DRG) neurons has not been characterized. Melastatin-like transient receptor potential 2 (TRPM2) channel activation and inhibition in response to oxidative stress, ADP-ribose (ADPR), flufenamic acid (FFA) and 2-aminoethoxydiphenyl borate (2-APB) in DRG neurons are also not clear. We tested the effects of FFA and 2-APB on ADPR and rotenone-induced TRPM2 cation channel activation in DRG neurons of rats. DRG neurons were freshly isolated from rats and studied with the conventional whole-cell patch-clamp technique. Rotenone, FFA and 2-APB were extracellularly added through the patch chamber, and ADPR was applied intracellularly through the patch pipette. TRPM2 cation currents were consistently induced by ADPR and rotenone. Current densities of the neurons were higher in the ADPR and rotenone groups than in control. The time courses (gating times) in the neurons were longer in the rotenone than in the ADPR group. ADPR and rotenone-induced TRPM2 currents were totally blocked by 2-APB and partially blocked by FFA. In conclusion, TRPM2 channels were constitutively activated by ADPR and rotenone, and 2-APB and FFA induced an inhibitory effect on TRPM2 cation channel currents in rat DRG neurons. Since oxidative stress is a common feature of neuropathic pain and diseases of sensory neurons, the present findings have broad application to the etiology of neuropathic pain and diseases of DRG neurons.     

Ellagic acid mitigates arsenic‐trioxide‐induced mitochondrial dysfunction and cytotoxicity in SH‐SY5Y cells

In the current study, neuroprotective significance of ellagic acid (EA, a polyohenol) was explored by primarily studying its antioxidant and antiapoptotic potential against arsenic trioxide (As₂O₃)‐induced toxicity in SH‐SY5Y human neuroblastoma cell lines. The mitigatory effects of EA with particular reference to cell viability and cytotoxicity, the generation of reactive oxygen species, DNA damage, and mitochondrial dynamics were studied. Pretreatment of SH‐SY5Y cells with EA (10 and 20 μM) for 60 min followed by exposure to 2 μM As₂O₃ protected the SH‐SY5Y cells against the harmful effects of the second. Also, EA pre‐treated groups expressed improved viability, repaired DNA, reduced free radical generation, and maintained altered mitochondrial membrane potential than those exposed to As₂O₃ alone. EA supplementation also inhibited As₂O₃‐induced cytochrome c expression that is an important hallmark for determining mitochondrial dynamics. Thus, the current investigations are more convinced for EA as a promising candidate in modulating As₂O₃‐induced mitochondria‐mediated neuronal toxicity under in vitro system.