Hepatoprotective Effect of Grape Seed and Skin Extract Against Lithium Exposure Examined by the Window of Proteomics.

Context: The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. Lithium (Li) used as drug for many neurological disorders such as bipolar disorders. Objective: This study aims to assess lithium toxicity and to evaluate the hepatic-protective properties of a grape skin seed and extract (GSSE). Materials and methods: Twenty-four male Wistar rats were exposed for 30 days to either various lithium concentrations, GSSE alone, or lithium supplemented with GSSE. The proteomic analysis revealed alterations of liver protein profiles after lithium treatments that were successfully identified by mass spectrometry. Results: Lithium treatment induced an oxidative damage by the alteration of antioxidant enzymes activities such as superoxide dismutase, CAT, and Gpx. The regulated proteins are mainly involved in the respiratory electron transport chain, detoxification processes, ribosomal stress pathway, glycolysis, and cytoskeleton. Proteins were differentially expressed in a dose-dependent manner. Interestingly, GSSE reversed the situation and restored the level of liver proteins whose abundance was modified after lithium treatment, arguing for its protective activity. Conclusion: Our data demonstrated the ability of proteomic analysis to underline the toxicity mechanisms of lithium in animal models. Based on these results, GSSE may be envisaged as a nutritional supplement to weaken the liver toxicity of lithium.

Bleomycin-Induced Damage in Rat Lung: Protective Effect of Grape Seed and Skin Extract.

Introduction: Bleomycin is an effective chemotherapeutic agent with main side effects including lung fibrosis which limited its clinical use. The aim of this study is to evaluate the protective effect of grape seed and skin extract (GSSE) against bleomycin-induced oxidative damage and inflammation in rat lung, by assessing respiratory index (RI), oxidative and nitrosative stress (SOD and XO activity, NO), fibrotic mediators (hydroxyproline and collagen), apoptosis (cytochrome C and LDH), inflammation (IL-6, TNF-α and TGF-ß1), and histological disturbances. Methods: Rats were pre-treated during three weeks with vehicle [ethanol 10% control] or GSSE (4 g/kg) and then administered with a single dose of bleo (15 mg/kg bw) at the 7th day.Results: Bleo disturbed lung function through the accumulation of hydroxyproline and collagen, decreased SOD activity but increased XO activity as well as GSH and NO levels. Bleo also increased the pro-inflammatory cytokines IL-6, TNF-α, and TGF-ß1, and pro-apoptotic cytochrome C factor and induced severe histological alterations of lung parenchyma. Interestingly GSSE pre-treatment efficiently counteracted most of the bleo-induced lung tissue damages. Conclusion: Data suggest that GSSE exerts anti-oxidant, ant-inflammatory, and anti-fibrosis properties that could find potential application in the protection against bleo-induced lung fibrosis.

Protective effect of the Spirulina platensis against toxicity induced by Diuron exposure in Mytilus galloprovincialis.

Diuron herbicide is widely used for weeds control in many kinds of cultivations. It reaches the waterbodies through various fate routes and can adversely threaten non-target organism. The current study was carried out to evaluate the antioxidant activity of Spirulina as feed additive against the toxicity of Diuron concentrations (40 and 80 µg/L) on the edible mollusk Mytilus galloprovincialis during seven days of exposure. Oxidative stress biomarkers were applied on mussel gills and digestive gland, investigating changes in enzymes activities such as catalase (CAT), Glutathione-S-transferase (GST) and Acetylcholinesterase (AChE) and the Malondialdehyde level (MDA). The obtained results show that diuron altered oxidative stress biomarkers in both organs, gills and digestive gland. Performed principle component analysis (PCA) highlighted relationship between biomarkers involved in functional response. Spirulina platensis supplemented diet (1 mg/L), completely ameliorated diuron-induced oxidative stress in mussel tissues. Thus, Spirulina seems to be a promising microalgae and eco-friendly tool helping the health recovery of aquatic animals subjected to environmental stressors.

This study provided recent and new data on the impact of Diuron in marine bivalve and the protective effect of Spirulina against Diuron-induced oxidative stress. The results of our study suggest that the antioxidant potential of Spirulina should be strongly candidate for the phytoremediation of Diuron-aquatic contaminated.

Ethinylestradiol (EE2) residues from birth control pills impair nervous system development and swimming behavior of zebrafish larvae.

The ubiquitous use of ethinylestradiol (EE2), an active constituent of birth control preparations, results in continuous release of this synthetic estrogen to surface waters. Many studies document the untoward effects of EE2 on the endocrine system of aquatic organisms. Effects of environmental EE2 on the nervous system are still poorly documented. We studied effects of pico- to nanomolar concentrations of EE2 on early nervous system development of zebrafish larvae. EE2 disrupted axonal nerve regeneration and hair cell regeneration up to 50%. Gene expression in larval brain tissues showed significantly upregulated expression of target genes, such as estrogen and progesterone receptors, and aromatase B. In contrast, downregulation of the tyrosine hydroxylase, involved in the synthesis of neurotransmitters, occurred concomitant with diminution of proliferating cells. Overall, the size of exposed fish larvae decreased by 25% and their swimming behavior was modified compared to non-treated larvae. EE2 interferes with nervous system development, both centrally and peripherally, with negative effects on regeneration and swimming behavior. Survival of fish and other aquatic species may be at risk in chronically EE2-contaminated environments.

Au-TiO2 nanoparticles exposure induced oxidative stress and neurotoxicity in rat.

CONTEXT: The Au-TiO2NPs have a wide range of applications and can easily enter the cells. Due to their properties, they can cause toxicity. OBJECTIVE: It was aimed to test the toxic effects of Au-TiO2 NPs in the brain, heart, kidney and liver of rats in this work. MATERIALS AND METHODS: All used rats in this work were treated using diverse concentrations (doses) of NPs (100 and 200 mg/kg bw) for 21 days. SOD, CAT, AChE activities and MDA, H2O2, NO contents were evaluated in different organs. RESULTS: The Au-TiO2 NPs exposure induced biochemical changes in different organs of rats in view of oxidative stress and neurotoxicity by the alteration of the activity of the enzyme of neurotransmitter (AChE activity). CONCLUSION: The Au-TiO2 NPs have the potential to interact with rat's biochemical status and cause undesirable effects. One of those damaging effects was oxidative stress and neurotoxicity. CLINICAL SIGNIFICANCE: The study signifies the impact of usage of Au-TiO2 NPs in the medical field for further exploration.

The protective effect of Hibiscus sabdariffa calyxes extract against cypermethrin induced oxidative stress in mice.

Cypermethrin (Cyp) is a kind of pyrethroids compound that is broadly used against different species of insects and pests. Cyp can also elicit a range of neurotoxic, immunotoxic, genotoxic and reproductive toxic effects on various experimental organisms. The aim of this study was to evaluate the protective effects of Hibiscus sabdariffa against the toxicity damage induced by Cyp exposure. The Hibiscus sabdariffa calyxes extract was given to mice (200-500 mg/kg bw). The mice, which were treated with Cyp and Hibiscus sabdariffa, were divided into six groups of six mice each. Groups I, IV and VI were used as control and groups II CYP control (20 mg/kg body weight)., groups III and V were treated with Hibiscus sabdariffa extract (200 and 500 mg/kg body weight) plus (20 mg/kg body weight) for 21 days Furthermore, HPLC was used to identify the compound fraction. This result showed Cyp -induced biochemical changes in all organs of mice. Cyp caused decreased CAT activity, inhibition of AChE activity and increased the levels of H2O2 and MDA in brain, heart, liver and kidney. Hibiscus sabdariffa exhibited antioxidant effect and significantly attenuated the neurotoxicity of Cyp. Hibiscus sabdariffa exhibits neuroprotective effects and can be an effective and novel alternative approach to reduce the risk caused by pyrethroid compound.

Protective effect of Zizyphus lotus jujube fruits against cypermethrin-induced oxidative stress and neurotoxicity in mice.

CONTEXT: Cypermethrin (CYP) is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control. The toxicity of CYP is well studied in many organisms. OBJECTIVE: The aim of present study was to investigate the protective effect of Zizyphus lotus (Zizyp) fruit against neurotoxicity and oxidative stress induced by CYP in mice. MATERIALS AND METHODS: Mice were divided into four groups of six each: groups I and II were used as control and CYP control (20 mg/kg body weight). While, groups III was orally treated with Zizyphus lotus fruit (5 g/kg body weight) plus CYP (20 mg/kg body weight) for 18 days. Furthermore, HPLC-ESI-MS-MS (Q-Tof) and GC-MS were used to identify the compounds fraction. RESULTS: Antioxidant enzyme catalase (CAT), neurotoxicity enzyme acetylcholinesterase (AChE) activities and hydrogen peroxide (H2O2), malondialdehyde (MDA) levels were determined in the liver, kidney and heart. CYP caused decreased CAT activity, inhibition of AChE activity and increased the levels of H2O2 and MDA in heart, liver and kidney. CONCLUSION: Our results indicate that Zizyp fruit is markedly effective in protecting mice against CYP-induced biochemical changes. This protection may be due to its antioxidant property and scavenging ability against active free radicals.

Lithium induced oxidative damage and inflammation in the rat's heart: Protective effect of grape seed and skin extract.

Lithium (Li) is a relevant mood stabilizer metal for the treatment of bipolar disorder (BD), as it protects from both depression and mania and reduces the risk of suicide. However, Lihas some clinical concerns as a narrow therapeutic index requiring routine monitoring of the serum level. The present study was designed to analyze the cardio-toxic side effect of Li and the ability of grape seed and skin extract (GSSE) to protect the heart against such toxicity. After 30days of exposure to Li (0, 2, 5 and 100mg/kg bw) and prevention with GSSE (4000mg/kg bw), rats were killed by decapitation and their heart processed for Li-induced oxidative stress. Data mainly showed that Li increased lipoperoxidation and protein carbonylation, it decreased superoxide dismutase and glutathione peroxidase activities, altered acetylcholinesterase (AChE) activity and increased the pro-inflammatory cytokine interleukin 6 (IL-6). Interestingly, GSSE efficiently alleviated all the deleterious effects of Li especially in low therapeutic doses. Based on our results, GSSE could be proposed as a nutritional supplement to mitigate the cardiotoxic side effects of lithium.

Neuroprotective Activity of Grape Seed and Skin Extract Against Lithium Exposure Using Proteomic Research.

Lithium (Li) has raised scientific concern because it represents a serious problem threatening human health. This study aimed firstly at analyzing and potentially quantifying the impact of Li and grape seed and skin extract (GSSE) separately and, secondly, describing the possible neuroprotective activity of GSSE against Li toxicity. To this end, rats were exposed for 30 days to different Li concentrations (0, 2, and 100 mg/kg bw), to GSSE (4000 mg/kg bw), and to binary mixture of Li and GSSE. Liquid chromatography (HPLC-MS/MS) analysis used for GSSE showed that 15 phenolic compounds are present in the extract. Significant modifications of proteins were detected in the brain using proteomics research after treatment. Proteins were successfully identified by a linear ion trap-Orbitrap mass spectrometer. These proteins can be roughly related to oxidative stress, glycolysis, signaling pathway, and inflammation. Additionally, proteins involved in cell junction such as myosin, spectrin, tubulin, ERM-binding phosphoprotein, and dynein were also affected by Li exposure. Dose response was detected for most expressed proteins after Li treatment. In contrast, GSSE induced the expression and/or the stabilization of some proteins changed after Li treatment in the brain showing its neuroprotective activity. These data demonstrate that proteomic analysis is a powerful tool to provide valuable insights into mechanisms of toxicity of Li in the nervous system of Wistar rats. To our knowledge, this is the first evidence of using GSSE as neuroprotective model against Li toxicity. These findings provide impetus for future investigation on GSSE against other toxic chemicals.