Toxicological assessment of sodium benzoate in Drosophila melanogaster.

Sodium benzoate (SB), the sodium salt of benzoic acid, is a food preservative with wide applications in the food, cosmetic and pharmaceutical industries due to its ability to kill many microorganisms effectively. Experimental evidence however suggests that excessive intake of SB poses detrimental health risks among consumers in the population. The present study investigated the toxic effects of various concentrations of SB using Drosophila melanogaster as a model. Adult wild-type flies of Canton S strain (1- to 3-days old) was orally exposed to SB (0, 0.5, 1.0, 2.0 and 5.0 mg/5 g diet) to evaluate survival rates for 21 days. Thereafter, we evaluated markers of oxidative stress, antioxidant status and behavioral activity in D. melanogaster exposed to SB for seven (7) days. We observed that SB (2.0 and 5.0 mg/5 g diet) decreased the survival of D. melanogaster. Also, SB inhibited glutathione-S-transferase activity and depleted total thiols and nonprotein thiols contents. Moreover, SB (5 mg/5 g diet) increased nitric oxide (nitrite/nitrate) level and reduced flies' emergence rate. Conclusively, findings from this study revealed that exposure to high concentrations of SB reduced survival rate and induced toxicity via the induction of oxidative stress and inhibition of antioxidant enzymes in D. melanogaster.

Vitellaria paradoxa inhibits arsenic-induced toxicity in Drosophila melanogaster via the augmentation of antioxidant system.

The Ethyl Acetate Fraction (EACF) of Ethanol Leaf Extract of Vitellaria paradoxa (ELVp) was assessed against Sodium Arsenite (SA)-induced toxicity in Drosophila melanogaster. The Gas Chromatography-Mass Spectrometry (GC-MS) analysis of EACF was carried out. The molecular docking of the compounds obtained from GC-MS was performed against D. melanogaster glutathione-S-transferase-2 (GST-2). Firstly, D. melanogaster (Harwich strain) was treated with EACF to determine its effect on longevity. Secondly, D. melanogaster was fed with EACF (1.0 and 3.0 mg/5 g diet) and/or SA (0.0625 mM) for 5 days. Thereafter, the ameliorative role of EACF in SA-induced toxicity was evaluated using the fly's emergence rate, locomotor activity, oxidative stress and antioxidant biomarkers. The in-silico study revealed varying degrees of binding affinity of the twelve active compounds of EACF against GST-2 which was comparable with the co-crystalized ligand (glutathione). The EACF increased the longevity of D. melanogaster by 20.0 % compared with control and ameliorated SA-induced reduction of emergence rate and locomotor performance by 178.2 and 20.5 %, respectively. Additionally, EACF ameliorated SA-induced reduction of total thiol and non-protein thiols and inhibition of catalase and GST activities (p < 0.05). These results corroborated with histological data obtained in the fat body of D. melanogaster. Overall, EACF augmented the antioxidant system of D. melanogaster and prevented sodium arsenite-induced oxidative stress due to its high antioxidant property.

Neurotoxic and behavioral deficit in Drosophila melanogaster co-exposed to rotenone and iron.

Exposure to environmental toxicants has been linked with the onset of different neurodegenerative diseases in animals and humans. Here, we evaluated the toxic effects of co-exposure to iron and rotenone at low concentrations in Drosophila melanogaster. Adult wild-type flies were orally exposed to rotenone (50.0 µM) and ferrous sulfate (FeSO4; 1.0 and 10.0 µM) through the diet for 10 days. Thereafter, we evaluated markers of oxidative damage (Hydrogen Peroxide (H2O2), Nitric Oxide (NO), Protein Carbonyl, and malondialdehyde (MDA)), antioxidant status (catalase, Glutathione S-Transferase (GST), Total Thiol (T-SH) and Non-protein Thiol (NPSH), neurotransmission (monoamine oxidase; MAO and acetylcholinesterase, AChE) and mitochondrial respiration. The results indicated that flies fed rotenone and FeSO4 had impaired locomotion, reduced survival rate, and AChE activity with a corresponding increase in MAO activity when compared with the control (p < 0.05). Furthermore, rotenone and FeSO4 significantly decreased the antioxidant status with a concurrent accumulation of NO, MDA, and H2O2. Additionally, the activity of complex 1 and mitochondria bioenergetic capacity was compromised in the flies. These findings suggest that the combination of rotenone and FeSO4 elicited a possible synergistic toxic response in the flies and therefore provided further insights on the use of D. melanogaster in toxicological studies.

Carcinogen sodium arsenite disrupts antioxidant and redox homeostasis in Drosophila melanogaster.

OBJECTIVES: The inadvertent exposure to environmental contaminants has been reported to induce cancer in different animal models. Here, we investigated the toxicity of Sodium Arsenite (SA), a Class I Carcinogen in Drosophila melanogaster. METHODS: Harwich fly strain (1-3 days old) of both sexes were orally exposed to SA (0, 0.0312, 0.0625 and 0.125 mM) for 14 days for survival study. Thereafter, 5 days exposure period was selected to assess the toxic effects of SA on oxidative stress and antioxidant markers. RESULTS: The results indicated that SA induced significant reduction in survival and emergence rate of flies. Furthermore, SA significantly increased Nitric Oxide (NO, nitrite and nitrate) and Hydrogen Peroxide (H2O2) levels in flies compared with control (p<0.05). In addition, SA inhibited catalase and glutathione-S-transferase (GST) activities, and depleted total thiol and glutathione (GSH) contents. Moreover, acetylcholinesterase activity significantly increased in flies treated with SA when compared with control. CONCLUSIONS: Sodium arsenite-induced reduction in survival and emergence rates of flies occurred via the disruption of oxidative stress-antioxidant homeostasis in D. melanogaster.

Mechanisms underpinning Carpolobia lutea G. Don ethanol extract's neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia.

ETHNOPHARMACOLOGICAL RELEVANCE: Persistent ketamine insults to the central nervous system block NMDA receptors and disrupt putative neurotransmission, oxido-nitrosative, and inflammatory pathways, resulting in schizophrenia-like symptoms in animals. Previously, the ethnomedicinal benefits of Carpolobia lutea against insomnia, migraine headache, and insanity has been documented, but the mechanisms of action remain incomplete. AIM OF THE STUDY: Presently, we explored the neuro-therapeutic role of Carpolobia lutea ethanol extract (C. lutea) in ketamine-induced schizophrenia-like symptoms in mice. MATERIALS AND METHODS: Sixty-four male Swiss (22 ± 2 g) mice were randomly assigned into eight groups (n = 8/group) and exposed to a reversal ketamine model of schizophrenia. For 14 days, either distilled water (10 mL/kg; p.o.) or ketamine (20 mg/kg; i.p.) was administered, following possible reversal treatments with C. lutea (100, 200, 400, and 800 mg/kg; p.o.), haloperidol (1 mg/kg, p.o.), or clozapine (5 mg/kg; p.o.) beginning on days 8-14. During the experiment, a battery of behavioral characterizations defining schizophrenia-like symptoms were obtained using ANY-maze software, followed by neurochemical, oxido-inflammatory and histological assessments in the mice brains. RESULTS: A 7-day reversal treatment with C. lutea reversed predictors of positive, negative and cognitive symptoms of schizophrenia. C. lutea also mitigated ketamine-induced neurochemical derangements as evidenced by modulations of dopamine, glutamate, norepinephrine and serotonin neurotransmission. Also, the increased acetylcholinesterase activity, malondialdehyde nitrite, interleukin-6 and tumor necrosis-factor-α concentrations were reversed by C. lutea accompanied with elevated levels of catalase, superoxide dismutase and reduced glutathione. Furthermore, C. lutea reversed ketamine-induced neuronal alterations in the prefrontal cortex, hippocampus and cerebellum sections of the brain. CONCLUSION: These findings suggest that C. lutea reverses the cardinal symptoms of ketamine-induced schizophrenia in a dose-dependent fashion by modulating the oxido-inflammatory and neurotransmitter-related mechanisms.

Ackee (Blighia sapida K.D. Koenig) Leaves and Arils Methanolic Extracts Ameliorate CdCl2-Induced Oxidative Stress Biomarkers in Drosophila melanogaster.

Different ethnomedical benefits have been documented on different parts of Ackee (Blighia sapida); however, their roles in ameliorating oxidative damages are not well established. CdCl2 inhibitory effects on some oxidative-stress biomarkers and ameliorative potentials of Ackee leaves (AL) and arils (AS) methanolic extracts were studied using Drosophila melanogaster as a model. One to 3-day-old D. melanogaster flies were orally exposed to different concentrations of CdCl2 in their diet for 7 days. The fly's survival profile and negative geotaxis assays were subsequently analysed. Methanolic extracts of AL and AS treatments showed negative geotaxis behaviour, and extracts were able to ameliorate the effect of Cd2+ on catalase and GST activities and increase total thiol and GSH levels, while it reduced the H2O2 generation (p ≤ 0.05) when compared to the control. Furthermore, Cd2+ exhibited noncompetitive and uncompetitive enzyme inhibition on catalase and GST activities, respectively, which may have resulted in the formation of Enzyme-substrate-Cd2+ transition complexes, thus inhibiting the conversion of substrate to product. This study, thus, suggests that the Cd2+ mechanism of toxicity was associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant imbalance, and that the AL and AS extracts possess essential phytochemicals that could alleviate possibly deleterious oxidative damage effects of environmental pollutants such as CdCl2. Thus, Ackee plant parts possess essential phytonutrients which could serve as valuable resources in heavy metal toxicity management.

An assessment of the rescue action of resveratrol in parkin loss of function-induced oxidative stress in Drosophila melanogaster.

Loss-of-function mutations in parkin is associated with onset of juvenile Parkinson's disease (PD). Resveratrol is a polyphenolic stilbene with neuroprotective activity. Here, we evaluated the rescue action of resveratrol in parkin mutant D. melanogaster. The control flies (w1118) received diet-containing 2% ethanol (vehicle), while the PD flies received diets-containing resveratrol (15, 30 and 60 mg/kg diet) for 21 days to assess survival rate. Consequently, similar treatments were carried out for 10 days to evaluate locomotor activity, oxidative stress and antioxidant markers. We also determined mRNA levels of Superoxide dismutase 1 (Sod1, an antioxidant gene) and ple, which encodes tyrosine hydroxylase, the rate-limiting step in dopamine synthesis. Our data showed that resveratrol improved survival rate and climbing activity of PD flies compared to untreated PD flies. Additionally, resveratrol protected against decreased activities of acetylcholinesterase and catalase and levels of non-protein thiols and total thiols displayed by PD flies. Moreover, resveratrol mitigated against parkin mutant-induced accumulations of hydrogen peroxide, nitric oxide and malondialdehyde. Resveratrol attenuated downregulation of ple and Sod1 and reduction in mitochondrial fluorescence intensity displayed by PD flies. Overall, resveratrol alleviated oxidative stress and locomotor deficit associated with parkin loss-of-function mutation and therefore might be useful for the management of PD.

Protective capacity of carotenoid trans-astaxanthin in rotenone-induced toxicity in Drosophila melanogaster.

Trans-astaxanthin (TA), a keto-carotenoid found in aquatic invertebrates, possesses anti-oxidative and anti-inflammatory activities. Rotenone is used to induce oxidative stress-mediated Parkinson's disease (PD) in animals. We probed if TA would protect against rotenone-induced toxicity in Drosophila melanogaster. Trans-astaxanthin (0, 0.1, 0.5, 1.0, 2.5, 10, and 20 mg/10 g diet) and rotenone (0, 250 and 500 µM) were separately orally exposed to flies in the diet to evaluate longevity and survival rates, respectively. Consequently, we evaluated the ameliorative actions of TA (1.0 mg/10 g diet) on rotenone (500 µM)-induced toxicity in Drosophila after 7 days' exposure. Additionally, we performed molecular docking of TA against selected pro-inflammatory protein targets. We observed that TA (0.5 and 1.0 mg/10 g diet) increased the lifespan of D. melanogaster by 36.36%. Moreover, TA (1.0 mg/10 g diet) ameliorated rotenone-mediated inhibition of Catalase, Glutathione-S-transferase and Acetylcholinesterase activities, and depletion of Total Thiols and Non-Protein Thiols contents. Trans-astaxanthin prevented behavioural dysfunction and accumulation of Hydrogen Peroxide, Malondialdehyde, Protein Carbonyls and Nitric Oxide in D. melanogaster (p < 0.05). Trans-astaxanthin showed higher docking scores against the pro-inflammatory protein targets evaluated than the standard inhibitors. Conclusively, the structural features of TA might have contributed to its protective actions against rotenone-induced toxicity.

Interactions and toxicity of non-essential heavy metals (Cd, Pb and Hg): lessons from Drosophila melanogaster.

Some heavy metals are essential in trace amounts, enhancing enzyme functioning and other intracellular molecules. Others are explicitly toxic at low concentrations, increasing the risk of organ-related toxicity. Non-essential metals have similar mechanisms of toxicity to essential metals. These include the modifiable change in oxidation states, interaction with sulfhydryl moieties of proteins and indirect modification of nucleic acids. Ultimately, oxidative stress is generated, and potentiation of damage ensues. The susceptibility, sensitivity, genetic resources, and cellular response of Drosophila melanogaster to heavy metal exposure and toxicity have made this insect appropriate for toxicological studies. In this review, we focus on the toxicological impacts of non-essential metals (Cd, Pb, and Hg) in Drosophila and discuss its cellular and developmental responses to increasing concentrations of these metals. We also suggest current or proposed therapeutic alternatives, as well as dimensions that may improve the studies of non-essential metal biology.

Methanol fraction of Ficus mucoso (welw) prevents iron-induced oxidative damage and alters mitochondrial dysfunction in Drosophila melanogaster.

The present study investigated the antioxidant and cyto-/mito-protective roles of Methanol Fraction of Ficus mucoso (MFFM) in iron-induced oxidative damage in Drosophila melanogaster. At first, 10-day survival rates were carried out separately on FeSO4 and MFFM, respectively, after which ameliorative effects of MFFM were investigated on FeSO4-induced toxicity for 5 days using biochemical and behavioral markers. Additionally, mitochondria were isolated from treated D. melanogaster to assess mitochondrial Permeability Transition (mPT) pore opening. The results showed that FeSO4 significantly reduced survival rate, total thiol level and activities of catalase and glutathione-S-transferase in D. melanogaster. In addition, treatment with FeSO4 caused increased generation of H2O2, NO (nitrite/nitrates) and acetylcholinesterase (AChE) activity compared with control (p < 0.05). Conversely, MFFM restored FeSO4-induced inhibition of glutathione-S-transferase and catalase activities, as well as glutathione and total thiol levels. FeSO4-induced elevation of AChE activity as well as H2O2 and NO (nitrites/nitrates) levels were ameliorated by MFFM with improved climbing activity. Interestingly, MFFM prevented FeSO4-induced mitochondrial Permeability Transition (mPT) pore opening, and elevated mitochondrial ATPase activity and mitochondrial lipid peroxides generation in D. melanogaster. Taken together, our results demonstrated that iron impaired anti-stress defence capacity, altered behavioral functions, increased generation of mitochondrial malondialdehyde and activated opening of the mPT pore in D. melanogaster. Conversely, methanol fraction of F. mucoso protected against iron-induced cyto-/mito-toxic effects. F. mucoso possibly contain bioactive agents which might be useful in the management of disorders associated with oxidative stress induced by iron and or related metals.

Beneficial actions of esculentin-2CHa(GA30) on high sucrose-induced oxidative stress in Drosophila melanogaster.

Hyperglycaemia-induced oxidative stress plays a critical role in the development of diabetes and its complications. This study investigated actions of esculentin-2CHa(GA30) on high sucrose-induced oxidative stress in adult Drosophila melanogaster. Adult flies were exposed to diets containing graded concentrations of sucrose in the presence or absence of esculentin-2CHa(GA30) (5.0-10 µmol/kg diet) for 7 days. Effects of high sucrose diet and/or esculentin-2CHa(GA30) on survival and longevity of flies, and markers of oxidative stress, antioxidant status and glucose were assessed. High-sucrose diet (15-30%) and esculentin-2CHa(GA30) (5-10 µmol/kg diet) enhanced the percentage of surviving flies by 33.5%-46.2% (P < 0.01) and 7.4%-26.9% (P < 0.01) respectively. Concentration-dependent reduction in total thiol (19.3-51.3%, P < 0.01), reduced glutathione (22.6-54.9%, P < 0.05-0.01), catalase activity (36.8-57.3%, P < 0.05-0.01) and elevated glucose concentration (1.8-2.9-fold, P < 0.001) were observed in high sucrose-fed flies. Esculentin-2CHa(GA30) alone did not affect levels of total thiol, reduced glutathione, glucose and catalase activity. Improved survival (1.2-1.3-fold, P < 0.05-0.01) and longevity (1.3-fold) were observed in flies treated with the peptide (5.0 and 7.5 µmol/kg diet). Feeding on sucrose and esculentin-2CHa(1-30) (5.0 and 7.0 µmol/kg diet) for 7 days increased total thiol (2 - 3-fold, P < 0.001) and reduced glutathione (1.6-1.8-fold, P < 0.05) levels. Reduced catalase activity (21.4-36.4%, P < 0.01) and reduced glucose level (38.6-49.4%, P < 0.01) were observed in peptide-treated flies. Esculentin-2CHa(1-30) inhibited sucrose-induced generation of hydrogen peroxide (7.5-13.7%, P < 0.05) and nitric oxide (22.3-42.9%, P < 0.01) in adult flies. Overall, findings from this study offered further insights into the anti-oxidative properties of esculentin-2CHa(GA30).

Metallobiology and therapeutic chelation of biometals (copper, zinc and iron) in Alzheimer's disease: Limitations, and current and future perspectives.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent cause of cognitive impairment and dementia worldwide. The pathobiology of the disease has been studied in the form of several hypotheses, ranging from oxidative stress, amyloid-beta (Aß) aggregation, accumulation of tau forming neurofibrillary tangles (NFT) through metal dysregulation and homeostasis, dysfunction of the cholinergic system, and to inflammatory and autophagic mechanism. However, none of these hypotheses has led to confirmed diagnostics or approved cure for the disease. OBJECTIVE: This review is aimed as a basic and an encyclopedic short course into metals in AD and discusses the advances in chelation strategies and developments adopted in the treatment of the disease. Since there is accumulating evidence of the role of both biometal dyshomeostasis (iron (Fe), copper (Cu), and zinc (Zn)) and metal-amyloid interactions that lead to the pathogenesis of AD, this review focuses on unraveling therapeutic chelation strategies that have been considered in the treatment of the disease, aiming to sequester free and protein-bound metal ions and reducing cerebral metal burden. Promising compounds possessing chemically modified moieties evolving as multi-target ligands used as anti-AD drug candidates are also covered. RESULTS AND CONCLUSION: Several multidirectional and multifaceted studies on metal chelation therapeutics show the need for improved synthesis, screening, and analysis of compounds to be able to effectively present chelating anti-AD drugs. Most drug candidates studied have limitations in their physicochemical properties; some enhance redistribution of metal ions, while others indirectly activate signaling pathways in AD. The metal chelation process in vivo still needs to be established and the design of potential anti-AD compounds that bi-functionally sequester metal ions as well as inhibit the Aß aggregation by competing with the metal ions and reducing metal-induced oxidative damage and neurotoxicity may signal a bright end in chelation-based therapeutics of AD.

Ethanol exacerbates manganese-induced oxidative/nitrosative stress, pro-inflammatory cytokines, nuclear factor-κB activation, and apoptosis induction in rat cerebellar cortex.

Manganese (Mn) exposure is causing public health concerns as well as heavy alcohol consumption. This study investigates the mechanisms of neurotoxicity associated with Mn and ethanol (EtOH) exposure in the rat cerebellar cortex. Experimental animals received 30 mg/kg of Mn alone, 5 g/kg of EtOH alone, co-exposed with 30 mg/kg of Mn and 1.25 or 5 g/kg EtOH, while control animals received water by oral gavage for 35 days. Subsequently, alterations in the neuronal morphology of the cerebellar cortex, oxidative/nitrosative stress, acetylcholinesterase (AChE) activity, neuro-inflammation and protein expression of p53, BAX, caspase-3, and BCL-2 were investigated. The results indicate that Mn alone and EtOH alone induce neuronal alterations in the cerebellar cortex, decrease glutathione level and antioxidant enzyme activities, along with an increase in AChE activity, lipid peroxidation, and hydrogen peroxide generation. Mn alone and EtOH alone also increased neuro-inflammatory markers, namely nitric oxide, myeloperoxidase activity, interleukin-1ß, tumor necrosis factor-α, and nuclear factor-κB (NF-κB) levels in the cerebellar cortex. Immunohistochemistry analysis further revealed that exposure of Mn alone and EtOH alone increases the protein expression of cyclooxygenase-2, BAX, p53, and caspase-3 and decrease BCL-2 in the rat cerebellar cortex. Furthermore, the results indicated that Mn co-exposure with EtOH at 1.25 and 5 g/kg EtOH significantly (p ≤ .05) increases the toxicity in the cerebellum when compared with the toxicity of Mn or EtOH alone. Taken together, co-exposure of Mn and EtOH exacerbates neuronal alterations, oxidative/nitrosative stress, AChE activity, pro-inflammatory cytokines, NF-κB signal transcription, and apoptosis induction in the rat cerebellar cortex.

Luteolin-Supplemented diets ameliorates Bisphenol A-Induced toxicity in Drosophila melanogaster.

Bisphenol A (BPA) is an industrial chemical used in the production of various plastic materials. It is associated with reproductive, immunological and neurological disorders. Luteolin, a flavonoid found in fruits and vegetables, possesses anti-oxidative, anti-inflammatory and free radical scavenging properties. Here, we carried out studies to ascertain if Luteolin would ameliorate BPA-induced toxicity in Drosophila melanogaster. Firstly, flies were treated separately with Luteolin (0, 50, 100, 150 and 300 mg/kg diet) and BPA (0, 0.01, 0.05 and 0.1 mM) for 28 days survival assessments. Consequently, Luteolin (150 and 300 mg/kg diet) and/or BPA (0.05 mM) were exposed to D. melanogaster for 7 days for the evaluation of nitric oxide level, eclosion rate, viability assay, histology of fat body, antioxidant (Glutathione-S-transferase, catalase and total thiol), oxidative stress (hydrogen peroxide) and behavioural (negative geotaxis and acetylcholinesterase) markers. The results showed that BPA induced antioxidant-oxidative stress imbalance and behavioural deficit in flies. Luteolin increased survival rate and augmented antioxidant markers in flies. Importantly, Luteolin ameliorated BPA-induced degeneration in the fat body around the rostral, thorax and abdominal regions, oxidative stress, behavioural deficit, reduction in cell viability and eclosion rate of D. melanogaster (p < 0.05). Overall, this study offered further insights on the antioxidative and chemopreventive properties of Luteolin against BPA-induced toxicity.

Rescue role of hesperidin in 4-vinylcyclohexene diepoxide-induced toxicity in the brain, ovary and uterus of wistar rats.

Background The ovotoxicity of 4-vinylcyclohexene diepoxide (VCD) has been established in several experimental models. Hesperidin (HSD) is a bi-flavonoid found in citrus fruits and has been reported to be a potent antioxidant and anti-inflammatory agent. Here, we have evaluated the rescue role of hesperidin on VCD-induced toxicity in the brain, ovary, and uterus of rats. Methods Six groups of rats containing ten rats in each group were orally given corn oil (control), hesperidin (100 mg/kg), hesperidin (200 mg/kg), VCD (250 mg/kg), VCD [(250 mg/kg)+hesperidin (100 mg/kg)] and VCD [(250 mg/kg)+hesperidin (200 mg/kg)] once a day for 30 days, respectively. Thereafter, we determined the selected biomarkers of oxidative damage, inflammation, endocrine balance, and histology of the reproductive organs. Results The data showed that hesperidin rescued VCD-induced increase in oxidative stress (hydrogen peroxide and malondialdehyde) and inflammatory (nitric oxide) biomarkers. In addition, hesperidin restored the reduction in antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase) activities and glutathione level in the brain, ovary, and uterus of rats (p<0.05). Lastly, hesperidin preserved the histological structure of the ovary and uterus of rats exposed to VCD. Conclusions Overall, the rescue role of hesperidin on VCD-induced toxicity in the brain and reproductive organs of female rats may be due to its antioxidative and anti-inflammatory properties.

Curcumin attenuates copper-induced oxidative stress and neurotoxicity in Drosophila melanogaster.

Curcumin is a hydrophobic polyphenol derived from the rhizome of the Herb Curcuma longa belonging to the family Zingiberaceae. Curcumin possesses antioxidative, anti-inflammatory and anti-depressant-like properties. In this study, we evaluated the rescue role of Curcumin in Copper2+-induced toxicity in D. melanogaster. Adult, wild type flies were exposed to Cu2+ (1 mM) and/or Curcumin (0.2 and 0.5 mg/kg diet) in the diet for 7 days. The results indicated that Cu2+- fed flies had reduced survival compared to the control group. Copper toxicity was also associated with a marked decrease in total thiol (T-SH), as well as catalase and glutathione S-transferase activities, contemporaneous with increased acetylcholinesterase (AChE) activity, nitric oxide (nitrate and nitrite) and dopamine levels. Co-exposure of flies to Cu2+ and Curcumin prevented mortality, inhibited AChE activity and restored dopamine to normal levels (p < 0.05). Moreover, Curcumin restored eclosion rates, and the cellular antioxidant status, as well as alleviated the accumulation of nitric oxide level in the flies. Curcumin ameliorated oxidative damage in the flies as evidenced by the survival rates, longevity assay as well as the restoration of antioxidant status. Our findings thus suggest that Curcumin ameliorated Cu2+-induced neurotoxicity in D. melanogaster and as such could be considered an effective therapeutic agent in the prevention and treatment of disorders, where oxidative stress is implicated.

Ethanol Exacerbates Manganese-Induced Neurobehavioral Deficits, Striatal Oxidative Stress, and Apoptosis Via Regulation of p53, Caspase-3, and Bax/Bcl-2 Ratio-Dependent Pathway.

This study investigated the effects of ethanol (EtOH) on manganese (Mn)-induced striatal toxicity in rat by evaluating the neurobehavioral changes, biochemical and molecular events in rats exposed to Mn alone at 30 mg/kg, or their combination with EtOH at 1.25- and 5-g/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were assessed using a video tracking software (ANY-Maze software) during a 5-min trial in a novel environment. Subsequently, acetylcholinesterase (AChE) activity, oxidative stress markers, histological morphology, and expression of apoptotic proteins (p53 and Bax and caspase-3) and anti-apoptotic protein (Bcl-2) were assessed in the striatum. Results showed that Mn, EtOH, and their combination induced locomotor and motor deficits. Track plot analysis indicated that EtOH exacerbated the Mn-induced reduction in exploratory profiles of exposed rats. Similarly, exposure of rats to Mn, EtOH, or combination of Mn and EtOH resulted in decreased activities of anti-oxidant enzymes, diminished level of reduced glutathione, downregulated Bcl-2 expression, increased AChE activity, enhanced hydrogen peroxide and lipid peroxidation levels, and upregulated expressions of p53, Bax, and caspase-3. Moreover, potentiation of Mn-induced striatal toxicity by EtOH co-exposure was dose dependent. Taken together, it seems that EtOH exacerbates Mn-induced neurobehavioral deficits, oxidative stress, and apoptosis induction via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway in rat striatum.

Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster.

1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) is a neurotoxin that causes Parkinson's disease in animals via mechanisms linked with oxidative stress and inflammation. Resveratrol is a natural polyphenol and a phytoalexin with antioxidative and antiinflammatory properties. Here, we investigated the rescue role of resveratrol on MPTP-triggered toxicity in Drosophila melanogaster for the first time. D. melanogaster (Harwich strain, 1-to 3- days old) were first orally exposed to resveratrol (0, 7.5, 15, 30, 60 and 120 mg/kg diet) and MPTP (0, 250, 500, 1000, 2000, and 3000 µM) for longevity and 7 days survival assays respectively. Consequently, we selected resveratrol (30 and 60 mg/kg diet) to evaluate its rescue role on MPTP (250 and 500 µM)-induced toxicity in D. melanogaster after 3 days of oral treatment. Specifically, we evaluated markers of neurotoxicity (acetylcholinesterase and negative geotaxis), inflammation (nitric oxide), oxidative stress-antioxidant status (hydrogen peroxide, total thiol, catalase and glutathione-S-transferase), cell viability and fecundity. The data showed that resveratrol increased lifespan of D. melanogaster in a dose-dependent manner up to 60 mg/kg diet. Further, resveratrol restored MPTP-induced inhibition of catalase, glutathione-S-transferase and acetylcholinesterase activities in D. melanogaster. Moreover, resveratrol ameliorated MPTP-triggered cell death, histological alterations, behavioural deficits and accumulation of nitric oxide and hydrogen peroxide levels in flies (p < 0.05). Conclusively, the lifespan extension effects of resveratrol and its rescue role on MPTP- mediated toxicity in the flies may be due to its antioxidant and anti-inflammatory properties.

Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats.

Chlorpyrifos (CPF) is an organophosphorus pesticide widely used in agricultural applications and household environments. 6-Gingerol-rich fraction from Zingiber officinale (Ginger, 6-GRF) has been reported to possess potent anti-oxidative, anti-inflammatory and anti-apoptotic properties. Here, we investigated the protective properties of 6-GRF on CPF-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Five groups of rats containing 14 rats/group received corn oil (control), CPF (5 mg/kg), 6-GRF (100 mg/kg), CPF (5 mg/kg) + 6-GRF (50 mg/kg) and CPF (5 mg/kg) + 6-GRF (100 mg/kg) through gavage once per day for 35 days respectively. The results showed that 6-GRF protected against CPF-induced increases in oxidative stress ((hydrogen peroxide (H2O2) and malondialdehyde (MDA)), inflammatory (myeloperoxidase (MPO), nitric oxide (NO) and tumour necrosis factor-α (TNF- α)), and apoptotic (caspase-3) markers. Also, 6-GRF improved the activities of antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) as well as glutathione (GSH) level in the brain, ovary and uterus of rats exposed to CPF (p < 0.05). Overall, the protective effects of 6-GRF on CPF-induced toxicity in the brain and reproductive organs of rats may be due to its potent antioxidative, anti-inflammatory and antiapoptotic properties.