ABSTRACT
OBJECTIVE: Given the noteworthy implications of alcohol consumption and its association with male infertility, there has been a notable focus on investigating natural alternatives to mitigate its adverse effects. Thus, this study was conducted to assess the potential protective effect of phycocyanin extract derived from the blue algae Arthrospira (Spirulina) platensis against ethanol-induced oxidative stress, disturbances in testicular morphology, and alterations in sperm production. METHODS: Male rats were divided into four groups (five rats each): the control group received a saline solution, the ethanol exposed group (EtOH) was subjected to intraperitoneal injections of 10 mL/kg of ethanol solution at a concentration of 38% (v/v), the phycocyanin alone treated group (P) received oral administration of phycocyanin at a dosage of 50 mg/kg, and the phycocyanin-cotreated group (PE) was given oral phycocyanin followed by ethanol injections. All treatments were administered over a period of 14 days. RESULTS: Our findings demonstrated that ethanol exposure induced reproductive toxicity, characterized by reduced sperm production and viability, alterations in testicular weight and morphology, increased lipid peroxidation levels, and elevated oxidative enzyme activity. In addition, the ethanol-intoxicated group showed perturbations in serum biochemical parameters. However, the simultaneous exposure to ethanol and phycocyanin exhibited a counteractive effect against ethanol toxicity. CONCLUSION: The results showed that supplementation of phycocyanin prevented oxidative and testicular morphological damage-induced by ethanol and maintained normal sperm production, and viability.
ABSTRACT
We studied the effect of Ajuga iva leaves extract (AIE) on the intestinal absorption, motricity and its antioxidant capacity against diarrhea. Wistar rats were divided and received either: castor oil (CO), CO and loperamide or CO and different doses of AIE. AIE prevented dose-dependently CO-induced diarrhea. AIE at 800 mg/kg showed inhibition efficiency on defecation and diarrhea. The pro-oxidant effect of the CO in the small intestine was inhibited significantly in presence of AIE: increasing glutathione peroxidase (GPx) activity and lowering oxygen free radicals (OH°, O2°-), carbonyl protein and malondialdehyde (MDA) levels. However, co-administration of AIE in castor oil-exposed groups significantly increased the intestinal contents of calcium and magnesium. AIE exhibits significant anti-diarrheal activity, related in part to its antioxidant properties. Our investigation also provides experimental evidence for the traditional use of this medicinal plant in the treatment of diarrhea.
ABSTRACT
INTRODUCTION: Oxidative stress has been implicated in the pathogenesis of diverse disease states. The present study was designed to examine the effects of magnesium sulphate (MgSO4) against hydrogen peroxide (H2O2) induced behaviour impairment and oxidative damage in rats. MATERIAL AND METHODS: Eighteen rats were equally divided into three groups. The first group was kept as a control. In the second group, H2O2 was given in drinking water at 3% during 5 days. In the third group, rats were subjected to daily administration of H2O2 and MgSO4 (100 mg/kg; b.w) for 5 days. Animals were subjected to behavioural tests (elevated plus maze and open field). At the end of experiment, brains were extracted for oxidative stress biomarkers assessment including levels of malondialdéhyde and hydrogen peroxide and activities of superoxide dismutase and catalase. RESULTS: Our findings showed that H2O2 treated rat exhibited anxiogenic behaviour and the genesis of free radicals in the brain. Magnesium showed amelioration against oxidative stress and significant decrease in anxiety levels. DISCUSSION AND CONCLUSION: Stress is a powerful process that disrupts brain homeostasis by inducing oxidative stress and its appear that magnesium may have potential therapeutic benefits by reducing oxidative stress and inducing anxiolytic effect.
Subject(s)
Hydrogen Peroxide , Neuroprotective Agents , Rats , Animals , Rats, Wistar , Antioxidants/pharmacology , Antioxidants/metabolism , Magnesium/pharmacology , Neuroprotective Agents/pharmacology , Oxidative Stress , Superoxide Dismutase/metabolismABSTRACT
The accumulation of relatively higher dose of zinc oxide nanoparticles in brain was reported to produce neurotoxicity. Indeed, nanoparticles have a high ability to penetrate biological membranes and be uptaken by cells, which may cause cell disorders and physiological dysfunctions. The aim of the current study was to evaluate, whether oral administration of saffron extract, in rats, can protect from neurotoxicity and behavioural disturbances induced by chronic administration of ZnO-NPs. Daily oral administration of ZnO-NPs was performed for 21 consecutive days to induce oxidative stress-like situation. Then after the saffron extract was concomitantly administrated in several rat groups to overcome the nanotoxicological effect induced by ZnO-NPs. In the frontal cortex, the hippocampus and the cerebellum, ZnO-NPs induced a H2 O2 -oxydative stress-like effect reflected in reduced enzymatic activities of catalase, superoxide dismutase and glutathione S-transferase, and decreased acetylcholinesterase activity. In addition, increased levels of proinflammatory interleukins IL-6 and IL-1-⺠occurred in the hippocampus, reveal the existence of brain inflammation. The concomitant administration of saffron extract to animals exposed to ZnO-NPs prevented the enhanced anxiety-related to the behaviour in the elevated plus-maze test, the open field test and preserved spatial learning abilities in the Morris water maze. Moreover, animals exposed to ZnO-NPs and saffron showed abnormal activity of several antioxidant enzymes as well as acetylcholinesterase activity, an effect that may underly the preserved anxiety-like behaviour and spatial learning abilities observed in these animals. Saffron extract has a potential beneficial therapeutic effect: antioxidant, anti-inflammatory and neuroprotective agent.
Subject(s)
Cognitive Dysfunction , Crocus , Metal Nanoparticles , Zinc Oxide , Rats , Animals , Antioxidants/metabolism , Zinc/pharmacology , Acetylcholinesterase/metabolism , Acetylcholinesterase/pharmacology , Crocus/metabolism , Zinc Oxide/toxicity , Metal Nanoparticles/toxicity , Oxidative Stress , Administration, OralABSTRACT
The objectives of the current study were to evaluate the Punica granatum root bark extract's (PGE) antioxidant and gastroprotective activities against ethanol-induced gastric ulcers in Wistar rats and to elucidate the putative mechanism of action using in silico analysis. The PGE phytochemical study shows high levels of phenolics, flavonoids, tannins, and polysaccharides. In vitro, the PGE was more effective at scavenging hydroxyl radicals than quercetin and had lower ferric reducing activity than catechin. In vivo, it was revealed that pretreatment of ethanol-ulcerated rats with PGE at oral doses of 100, 200, and 400 mg/kg b.w. offered a dose-dependent shield against ethanol-induced ulcers when compared to Omeprazole (20 mg/kg b.w.) by preventing the development of deep ulcer lesions, lowering gastric juice output and pH rises, boosting gastric mucus production and antioxidant enzyme levels, and attenuating malondialdehyde and myeloperoxidase contents. Moreover, the liquid chromatography-mass spectrometry analysis of PGE identified 5 phenolic acids and 4 flavonoids, which revealed an in silico high oral bioavailability, drug-likenesses, and good binding affinities and thus inhibitory effects on the gastric H+, K+-ATPase enzyme. PGE may have synergistic antioxidant, anti-inflammatory, and H+, K+-proton pump inhibitory actions that contribute to its antiulcer efficacy.
ABSTRACT
OBJECTIVE: Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. METHODS: Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. CONTROL GROUP: non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. RESULTS: Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. CONCLUSIONS: Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.
Subject(s)
Chemical and Drug Induced Liver Injury , Testosterone , Male , Rats , Animals , Testosterone/pharmacology , Rats, Wistar , Corn Oil , Hydrogen Peroxide , Orchiectomy , Oxidative Stress , Cognition , WaterABSTRACT
Silver nanoparticles (Ag-NPs) are extremely useful in a diverse range of consumer goods. However, their impact on the environment is still under research, especially regarding the mechanisms involved in their effect. Aiming to provide some insight, the present work analyzes the transcriptional activity of six genes (Hsp83, Hsp17.2, Hsp19.8, SOD Cu-Zn, Mn-SOD, and BPI) in the terrestrial snail Helix aspersa in the presence of different concentrations of Ag-NPs. The animals were exposed for seven days to Lactuca sativa soaked for one hour in different concentrations of Ag-NPs (20, 50, 100 mg/L). The results revealed that the highest concentration tested of Ag-NPs (100 mg/L) led to a statistically significant induction of the Hsp83 and BPI expression in the digestive gland compared to the control group. However, a trend to upregulation with no statistical significance was observed for all the genes in the digestive gland and the foot, while in the hemolymph, the trend was to downregulation. Ag-NPs affected the stress response and immunity under the tested conditions, although the impact was weak. It is necessary to explore longer exposure times to confirm that the effect can be maintained and impact on health. Our results highlight the usefulness of the terrestrial snail Helix aspersa as a bioindicator organism for silver nanoparticle pollution biomonitoring and, in particular, the use of molecular biomarkers of pollutant effect as candidates to be included in a multi-biomarker strategy.
Subject(s)
Biological Monitoring/methods , Environmental Pollutants/adverse effects , Helix, Snails/drug effects , Helix, Snails/genetics , Metal Nanoparticles/chemistry , Transcription, Genetic/drug effects , Animals , Antimicrobial Cationic Peptides/biosynthesis , Antimicrobial Cationic Peptides/genetics , Blood Proteins/biosynthesis , Blood Proteins/genetics , Environmental Biomarkers , Gene Expression Profiling , Heat-Shock Proteins/biosynthesis , Heat-Shock Proteins/genetics , Helix, Snails/immunology , Lactuca , Oxidative Stress/drug effects , Sentinel Species , Silver/pharmacology , Transcription, Genetic/geneticsABSTRACT
Styrene 7,8-oxide (SO) is the principal metabolite of styrene, an industrial neurotoxic compound which causes various neurodegenerative disorders. The present study aimed to explore the mechanisms of SO cytotoxicity (0.5 - 4 mM) in primary cortical neurons and to evaluate the neuroprotective potential of quercetin (QUER). Our results showed that exposure to SO decreased viability of cortical neurons in a concentration-dependent manner. In the presence of QUER, cell viability was increased significantly. The neuroprotective effects of QUER were associated with the reduction of intracellular Reactive Oxygen Species (ROS), the decrease in calcium overload and the restoration of mitochondrial membrane depolarization caused by SO. Additionally, to evaluate neuronal death mechanisms triggered by SO, cells were incubated with Ac-DEVD-CHO, Calpeptin and Necrostatin-1, pharmacological inhibitors of caspase-3, calpains and necroptosis respectively. The data showed that the three inhibitors reduced cell death induced by SO and suggested the implication of apoptotic, necrotic and necroptotic pathways. However, western blot analysis showed that QUER attenuated the activation of caspase-3 but did not prevent calpain activity. Taken together, these data indicated that the cytotoxicity of SO was mediated by oxidative stress and apoptosis, necrosis and necroptosis mechanisms, while the neuroprotection provided by QUER against SO depended mainly on its anti-apoptotic activity.
Subject(s)
Epoxy Compounds , Neurons , Neuroprotective Agents , Quercetin , Apoptosis , Caspase 3/metabolism , Epoxy Compounds/toxicity , Humans , Necrosis , Neurons/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress , Quercetin/pharmacology , Reactive Oxygen Species/metabolismABSTRACT
Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.
Subject(s)
Cerebrum/metabolism , Glial Fibrillary Acidic Protein/metabolism , HSP70 Heat-Shock Proteins/metabolism , Receptors, Glucocorticoid/metabolism , Animals , Biomarkers/metabolism , Cerebrum/radiation effects , Female , Gene Expression Regulation/radiation effects , Hippocampus/metabolism , Hippocampus/radiation effects , Hypothalamus/metabolism , Hypothalamus/radiation effects , Rats , Rats, Sprague-Dawley , Somatosensory Cortex/metabolism , Somatosensory Cortex/radiation effectsABSTRACT
We investigate the antioxidant activity and protective effects of the aqueous leaf extract of Pistacia lentiscus (AELPL) against ulcerative colitis induced by acetic acid infusion through the rectum in Wistar rats. Phytochemical analyses allowed the identification of numerous phenolic compounds in P. lentiscus leaves such as flavonoids (isoquercetin and luterolin), flavonols (catechin, rutin, and kaempferol), phenolic acids (ellagic and dicaffeoylquinic), and tanins. Acetic acid exposure induced macroscopic colonic mucosal lesions with hemorrhage, congestion, edema, and the development of an expected oxidative stress state revealed by an increase in lipoperoxidation and carbonylation of proteins and a decrease in sulfhydryl (SH) group levels and antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione-S-peroxidase, and glutathione transferase, as well as an increase in the inflammatory cytokine, interleukin-6, in the colon and plasma. Administration of acetic acid also increased plasma and tissue levels of hydrogen peroxide and rates of iron and free calcium, whereas AELPL significantly and dose-dependently attenuated all the previous biochemical alterations and intracellular mediator perturbations. In conclusion, the AELPL exhibited a potent cytoprotective effect against acetic acid-induced colitis in rats, mainly through its antioxidant and anti-inflammatory activities.
Subject(s)
Colitis, Ulcerative , Colitis , Pistacia , Acetic Acid/metabolism , Animals , Antioxidants/metabolism , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colitis, Ulcerative/metabolism , Colon/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Oxidative Stress , Plant Extracts/metabolism , Rats , Rats, WistarABSTRACT
PACAP-38 (P38) is a pleiotropic peptide that exerts multiple peripheral and central actions, including neurotrophic, neuroprotective and anti-inflammatory actions. Previous studies have suggested an improvement of memory in rats that have received a single systemic injection of P38. In a therapeutic perspective, we used an analog, acetyl-[Ala15, Ala20]PACAP-38-propylamide (ALG), to improve both stability and affinity for PAC1 receptors vs. endogen PACAP. We investigated the effect of P38 and ALG on memory consolidation using a spatial novelty detection (SND) task in which rats had to memorize a configuration of objects to identify that, during a test session, a familiar object has been moved to a new location. Rats received an intravenous injection of P38 or ALG after the last training session. In Experiment 1, P38 (30 µg/kg) improved spatial memory consolidation allowing detection of novelty vs. saline injection. In Experiment 2, we confirmed this effect and showed that P38 restored the performance similar to what was found using non-injected rats. This suggests that, contrary to ALG, P38 exerted a promesiant rather than an anxiety-related effect whereas ALG did not show similar action. We also examined whether P38 effect involved an interaction with NR2B-containing NMDA receptors (NMDARs) by administrating ifenprodil (IFE; a selective NR2B-containing NMDAR antagonist) alone or in combination with P38 or ALG. The results suggested that P38 action on memory involved NR2B-containing NMDARs. Lastly, brain-derived neutrophic factor (BDNF) modulation appeared to be not related to the behavioral performance in the SND task. Overall, the results indicate that P38 exerted a beneficial effect on memory consolidation in a non-associative task, whereas ALG did not have this action.
Subject(s)
Memory Consolidation/drug effects , Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology , Spatial Memory/drug effects , Animals , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Hippocampus/metabolism , Learning/drug effects , Male , Maze Learning/drug effects , Memory Consolidation/physiology , Pituitary Adenylate Cyclase-Activating Polypeptide/chemical synthesis , Pituitary Adenylate Cyclase-Activating Polypeptide/chemistry , Rats , Rats, Wistar , Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/drug effects , Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/metabolismABSTRACT
Carob (Ceratonia siliqua L.) contains a wide variety of polyphenols with high antioxidant properties. In this study, we investigated the effects of aqueous extract of carob pods (AECP) on emotional behavior impairments and metabolic disorders in ovariectomized (OVX) rats. Female Wistar rats were assigned to three groups: group 1, control non-OVX rats; group 2, OVX rats; and group 3, OVX rats orally treated with AECP (500 mg/kg) for15 days after ovariectomy. Elevated plus-maze and open-field tests were performed on the 26th and 27th post-ovariectomy days, respectively. Afterwards, the rats were anesthetized and their serums were collected for biochemical analysis. We found that AECP improved emotional behavior impairments revealed by elevated plus-maze and open-field tests in OVX rats. Moreover, ovariectomy significantly increased triglyceride, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels in the serum. AECP administration significantly reversed ovariectomy-induced biochemical alterations. Thus, we suggest that the AECP may have an anxiolytic-like effect and prevent biochemical disorders associated with menopause or ovariectomy.
Subject(s)
Behavior, Animal/drug effects , Emotions , Estrogens/deficiency , Galactans/pharmacology , Mannans/pharmacology , Metabolic Diseases/drug therapy , Plant Gums/pharmacology , Animals , Female , Ovariectomy , Rats , Rats, WistarABSTRACT
There is increasing scientific evidences that the physical and chemical properties of manufactured nanoparticles lead to an increase in their bioavailability and toxicity. Among them Copper oxide nanoparticles (CuO-NPs) are widely used in different fields. However their potential adverse effects namely on brain functions are still discussed. Thus, the present study aimed to investigate the subacute oral toxicity and effects of CuO-NPs on cognitive performances in rats. Rats were randomly divided into three groups of 8 animals each, a control group received a dose 9 sodium chloride and the other groups received a suspension of CuO-NPs at doses of 250 and 500 mg/kg through oral gavage for 14 consecutive days. Multiple behavioral tests showed that CuO-NPs caused little changes in memory and learning performances as well as the locomotors activity, while the anxiety index increased. Copper NPs exposure increased also the liver and stomach relative weights and altered some blood biochemical parameters.
Subject(s)
Cognition/drug effects , Copper/toxicity , Nanoparticles/toxicity , Administration, Oral , Animals , Male , Maze Learning , Nanoparticles/chemistry , Rats , Rats, WistarABSTRACT
OBJECTIVE: To evaluate the phospholipid profile in total plasma, non-high-density lipoprotein (HDL), and HDL fractions. We tried to correlate the phospholipid profile to low-density lipoprotein (LDL) size, as reflected by cholesterol content in each LDL subclass. METHODS: We measured small dense LDL-C levels after heparin-magnesium precipitation and measured high-density lipoprotein phospholipid (HDL-P) levels using a colorimetric enzymatic method. RESULTS: The correlation of the phospholipid profile to small dense LDL-C (sdLDL-C) in patients with coronary problems showed a negative association between small dense low-density lipoprotein (sdLDL) and HDL-P (r = -0.73; P = .02). Moreover, a strong positive correlation was detected between TG and the ratio HDL-P/HDL-C (r = 0.83; P <.001). CONCLUSIONS: HDL phospholipid has an antiatherogenic effect in coronary artery disease with or without diabetes. Further, large LDL modulation seems to be associated with diabetes rather than coronaropathy.
Subject(s)
Coronary Artery Disease/metabolism , Diabetes Mellitus/metabolism , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Adolescent , Adult , Aged , Cholesterol/blood , Coronary Artery Disease/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Male , Middle Aged , Phospholipids/blood , Tunisia/epidemiology , Young AdultABSTRACT
Iron Oxide Nanoparticles (IONPs) present unique properties making them one of the most used NPs in the biomedical field. Nevertheless, for many years, growing production and use of IONPs are associated with risks that can affect human and the environment. Thus, it is essential to study the effects of these nanoparticles to better understand their mechanism of action and the molecular perturbations induced in the organism. In the present study, we investigated the toxicological effects of IONPs (γ-Fe2O3) on liver, lung and brain proteomes in Wistar rats. Exposed rats received IONP solution during 7 consecutive days by intranasal instillation at a dose of 10 mg/kg body weight. An iTRAQ-based quantitative proteomics was used to study proteomic variations at the level of the three organs. Using this proteomic approach, we identified 1565; 1135 and 1161 proteins respectively in the brain, liver and lung. Amon them, we quantified 1541; 1125 and 1128 proteins respectively in the brain, liver and lung. Several proteins were dysregulated comparing treated samples to controls, particularly, proteins involved in cytoskeleton remodeling, cellular metabolism, immune system stimulation, inflammation process, response to oxidative stress, angiogenesis, and neurodegenerative diseases.
Subject(s)
Brain/drug effects , Ferric Compounds/administration & dosage , Liver/drug effects , Lung/drug effects , Metal Nanoparticles , Proteome , Proteomics , Animals , Biomarkers , Brain/metabolism , Liver/metabolism , Male , Proteomics/methods , Rats , Signal Transduction/drug effects , Toxicity Tests/methodsABSTRACT
Depression is a common mental disease affecting a lot of people of all ages around the world. Today, improving the therapeutic effects of currently used antidepressants such as clomipramine and, especially when they are administered at high doses is a topic of interest. The study aims to evaluate the eventual role of zinc (30 mg/Kg) in ameliorating clomipramine (75 mg/Kg) effects on behavior and oxidative stress equilibrium following a 6 day treatment in male Wistar rats. Our main findings showed that zinc improved clomipramine antidepressant and locomotor effects. Moreover, zinc reversed the oxidative stress induced by this drug in the liver. Thus, zinc at 30 mg/Kg may constitute an efficient adjuvant for clomipramine used at a high dose (75 mg/Kg) by boosting its efficacy on behavior and alleviating its negative effects on oxidative balance in liver.
Subject(s)
Locomotion/drug effects , Oxidative Stress/drug effects , Zinc/pharmacology , Animals , Antidepressive Agents/pharmacology , Clomipramine/pharmacology , Depression/drug therapy , Depressive Disorder/drug therapy , Disease Models, Animal , Male , Motor Activity/drug effects , Rats , Rats, Wistar , Stress, Psychological/drug therapy , Zinc/metabolismABSTRACT
Nanomaterials have gained much attention for their use and benefit in several fields. Iron Oxide Nanoparticles (IONPs) have been used in Biomedicine as contrast agents for imaging cancer cells. However, several studies reported the potential toxicity of those nanoparticles in different models, especially in cells. Therefore, in our present study, we investigated the effects of IONPs on the SH-SY5Y neuroblastoma cell line. We carried out cytotoxic and genotoxic studies to evaluate the phenotypic effects, and proteomic investigation to evaluate the molecular effects and the mechanisms by which this kind of NPs could induce toxicity. Our results showed that the use of three different sizes of IONPs (14, 22 and 30 nm) induced cell detachment, cell morphological changes, size, and concentration-dependent IONP internalization and cell mortality. IONPs induced slight genotoxic damage assayed by modified comet assay without affecting cell cycle, mitochondrial function, membrane integrity, intracellular calcium level, and without inducing ROS generation. All the studies were performed to compare also the effects of IONPs to the ferric iron by incubating cells with equivalent concentration of FeCl3. In all tests, the NPs exhibited more toxicity than the ferric iron. The proteomic analysis followed by gene ontology and pathway analysis evidenced the effects of IONPs on cytoskeleton, cell apoptosis, and cancer development. Our findings provided more information about IONP effects on human cells and especially on cancer cell line.
Subject(s)
Apoptosis/drug effects , DNA Damage , Ferric Compounds/toxicity , Nanoparticles/toxicity , Proteome/metabolism , Animals , Cell Cycle/drug effects , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Survival/drug effects , Comet Assay , Ferric Compounds/chemistry , Humans , Membrane Potential, Mitochondrial/drug effects , Nanoparticles/chemistry , Particle Size , Proteomics , Reactive Oxygen Species/metabolismABSTRACT
Iron Oxide Nanoparticles (IONPs) are used in several fields of application, mainly in the biomedical field for their magnetic properties and in food additive known as "E172" for their colour. In the present investigation, we focused on IONP effects on Wistar rat following acute oral exposure. We performed a multiscale physiopathological investigation in order to elucidate potential toxic effects linked to IONP ingestion, especially on cognitive capacities, trace element distribution, blood constituents, organ functions, organ structure and iron deposit. We demonstrated that oral exposure to IONPs induces disturbances of certain parameters depending on the dose. Interestingly, the histopathological examination evidenced inflammatory effects of IONPs in the liver with iron deposits in hepatocytes and Kuppfer cells. Neurobehavioral examination showed that oral exposure to IONPs did not affect nor rat emotions, exploration and locomotion capacities, nor spatial reference memory status. Furthermore, oral administration of IONPs did not disrupt the trace element homeostasis nor in the liver neither in the stomach. Altogether, our study evidenced low signs of toxicity, but some effects lead us to a careful use of these NPs. Thereby, their use in foods should be further studied to better evaluate the potential toxic risks of the oral exposure to IONPs.
Subject(s)
Cognition/drug effects , Dietary Exposure , Ferric Compounds/analysis , Ferric Compounds/pharmacokinetics , Metal Nanoparticles , Trace Elements/pharmacokinetics , Animals , Behavior, Animal/drug effects , Body Weight/drug effects , Clinical Chemistry Tests , Ferric Compounds/chemistry , Hematologic Tests , Homeostasis , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Metal Nanoparticles/chemistry , Organ Size/drug effects , Rats, Wistar , Tissue Distribution , Toxicity Tests, Acute/methodsABSTRACT
Several in vitro studies have convincingly demonstrated that SiO2NPs mediated cytotoxicity, which was dose-, time- and size-dependent. The data on in vivo toxicity of SiO2NPs are even more contradictory. In the present study, we investigated the effects of sub-acute exposure to SiO2-NPs on spatial learning and memory, the biochemical parameters and the histology of organs. Rats were injected intravenously with a single dose of SiO2-NPs (20 mg/kg) during five consecutive days. The analysis of spatial memory in the Morris water maze showed that SiO2-NPs disrupt the cognitive abilities of rats. Moreover, SiO2-NPs could changes the blood counts. However, biochemical markers remained unchanged. Histological examination showed that SiO2-NPs induced pathological changes in rat organs. In this finding NPs were shown to cause granuloma formation and inflammatory cells infiltration in the liver.
Subject(s)
Cognition/drug effects , Nanoparticles/poisoning , Silicon Dioxide/poisoning , Animals , Rats , Rats, WistarABSTRACT
This study investigated the effects of ferrous sulfate (FeSO4) on motor skills, hematological and biochemical parameters in rats. Adult rats were treated with dose of iron (280 mg/L, per os) for 15 consecutive days in drinking water. No significant difference was noticed for the motor skills in the stationary beam (p = 0.23) and suspended string tests (p = 0.48) between control and iron-treated rats. However, iron-treated rats showed a significant increase in white blood cells count (p = 0.01), mean corpuscular volume values (p = 0.02) and decrease in frequency of peristaltic contractions of the fragment of the intestine (in vitro) compared to control rats (p = 0.01). No significant difference in plasma iron level (p = 0.89) and transferrin amount were observed after iron treatment (p = 0.65). The findings indicate that iron treatment at 280 mg/L, per os for 15 consecutive days in adult rats induced increase of hematological parameters (sign of a potential inflammation), but not motor skills deficit.