Antidepressants- and antipsychotics-induced hepatotoxicity.

Drug-induced liver injury (DILI) is a serious health burden. It has diverse clinical presentations that can escalate to acute liver failure. The worldwide increase in the use of psychotropic drugs, their long-term use on a daily basis, common comorbidities of psychiatric and metabolic disorders, and polypharmacy in psychiatric patients increase the incidence of psychotropics-induced DILI. During the last 2 decades, hepatotoxicity of various antidepressants (ADs) and antipsychotics (APs) received much attention. Comprehensive review and discussion of accumulated literature data concerning this issue are performed in this study, as hepatotoxic effects of most commonly prescribed ADs and APs are classified, described, and discussed. The review focuses on ADs and APs characterized by the risk of causing liver damage and highlights the ones found to cause life-threatening or severe DILI cases. In parallel, an overview of hepatic oxidative stress, inflammation, and steatosis underlying DILI is provided, followed by extensive review and discussion of the pathophysiology of AD- and AP-induced DILI revealed in case reports, and animal and in vitro studies. The consequences of some ADs and APs ability to affect drug-metabolizing enzymes and therefore provoke drug-drug interactions are also addressed. Continuous collecting of data on drugs, mechanisms, and risk factors for DILI, as well as critical data reviewing, is crucial for easier DILI diagnosis and more efficient risk assessment of AD- and AP-induced DILI. Higher awareness of ADs and APs hepatotoxicity is the prerequisite for their safe use and optimal dosing.

Antioxidant Activity of Selected Polyphenolics in Yeast Cells: The Case Study of Montenegrin Merlot Wine.

Screens of antioxidant activity (AA) of various natural products have been a focus of the research community worldwide. This work aimed to differentiate selected samples of Merlot wines originated from Montenegro, with regard to phenolic profile and antioxidant capacity studied by survival rate, total sulfhydryl groups and activities of glutathione peroxidase (GPx), glutathione reductase and catalase in H2O2⁻stressed Saccharomyces cerevisiae cells. In this study, DPPH assay was also performed. Higher total phenolic content leads to an enhanced AA under both conditions. The same trend was observed for catechin and gallic acid, the most abundant phenolics in the examined wine samples. Finally, the findings of an Artificial Neural Network (ANN) model were in a good agreement (r² = 0.978) with the experimental data. All tested samples exhibited a protective effect in H2O2⁻stressed yeast cells. Pre-treatment with examined wines increased survival in H2O2⁻stressed cells and shifted antioxidative defense towards GPx⁻mediated defense. Finally, sensitivity analysis of obtained ANN model highlights the complexity of the impact that variations in the concentrations of specific phenolic components have on the antioxidant defense system.

Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells.

BACKGROUND: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. METHODS: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. RESULTS: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: 51TQINKVVR58, 85DILNQITKPNDVYSFSLASR104, 111YPILPEYLQCVKELYR126, 187AFKDEDTQAMPFR199, 277KIKVYLPR284, and 278IKVYLPR284. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1ß, IL-25, IL-33, TSLP and TNFα), while OVA modification with 10mM MDA induced down regulation of the cytokine expression profile, except for IL-1ß. OVA and OVA modified with 1mM MDA induced secretion of epithelial cells specific cytokine IL-33. CONCLUSIONS: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. GENERAL SIGNIFICANCE: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity.

Antioxidant and cytotoxic activity of red wine after in vitro simulated digestion in the presence of complex food matrix.

The beneficial effect of moderate wine consumption is attributed to its micronutrients, especially polyphenols and largely depends on the digestion process. This work aimed to examine the influence of in vitro simulated digestion in the presence of complex food matrix on antioxidant and cytotoxic activity of red wine. The obtained results showed that total phenolic content of wine sample after in vitro digestion was higher compared to undigested wine, while the antioxidant activity of these samples was similar before and after digestion. Furthermore, it has been noticed that digested wine showed cytotoxic activity on SKBR3 breast adenocarcinoma cells near 20% after 72 h of treatment. This pioneering study that examined biological potential of in vitro digested wine in the presence of complex food matrix indicate that antioxidant and cytotoxic activity of red wine is preserved after digestion.

Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes.

Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical's scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.

Multielement analysis and antioxidant capacity of Merlot wine clones developed in Montenegro.

The overall aim of this paper was to compare the multielement composition and antioxidant capacity of two Montenegrin Merlot wines obtained from specific vine clones (VCR1 and VCR 101) along with commercial Merlot wine throughout the consecutive vintages in 2010 and 2011. Elemental composition was analysed using inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). Additionally, antioxidant capacity was assessed by cyclic voltammetry. VCR 1 wine from 2011 stood out for its elemental composition. On the other hand, antioxidant capacity of VCR 101 wines was the highest one for the both vintages. According to the experimental data obtained, all three wines are good source of essential elements and products with a significant antioxidant activity and specific geographical origin.

Comparative analytical study of the selected wine varieties grown in Montenegro.

Samples of the selected red wine varieties grown in Montenegro (Merlot, Cabernet Sauvignon and Vranac; vintages 2010-2012) were compared according to total phenolic content, anti-DPPH radical activity, phenolic profile and elemental composition. All the samples showed profound anti-DPPH radical activity, due to high content of total phenolic compounds (R = 0.92). The most abundant phenolics were catechin and gallic acid with the highest values recorded for Merlot 2012 (43.22 and 28.65 mg/L, respectively). In addition to this, the content of essential elements including the potentially toxic ones was within healthy (safe) level for all the samples analysed. This study has actually pointed out Merlot wine variety as the best quality one, though all three varieties may be used as safe and health-promoting nutritional products.