Examination of Prooxidative Activity of Red Wine in Melanoma Cells

Melanoma is responsible for 75% of all deaths from skin cancer. Its lethality arises from its rapid progression, easy metastasis and drug-resistance as well. Red wine is a natural product rich in polyphenolic compounds with potent anticancer activities. It seems that in cancer cells these compounds behave as prooxidants initiating reactive oxygen species mediated cellular DNA breakage and consequent cell death. The aim of this study was to investigate prooxidative activity of red wine samples (Merlot variety, commercial as well as VCR1 and VCR101 clonal wines) in melanoma A375 cells, through measuring the relationship of reduced and oxidized form of glutathione (GSH/GSSG) and comparison with the GSH/GSSG ratio in control (untreated melanoma cells). The data obtained showed that tested red wine samples decrease GSH/GSSG ratio in A375 cells compared to control (4.6 ± 0), with the largest decrease noticed in treatment with VCR101 wine (0.66 ± 0.05)

Antioxidant Enzymes in Blood of Women With Uterine Hyperplasia

The literature emphasizes the involvement of oxidative stress in the etiopathogenesis of many uterine diseases. Antioxidant system (AOS) represents the protective mechanism used by cells to neutralize overproduced reactive oxygen species (ROS) and prevent oxidative stress. We have previously shown that in gynecological patients with various diagnoses, the reproductive and other factors may be associated with antioxidant capacity and the ability to defend against oxidative damage. In this study, we examined the changes in expression of antioxidant enzymes (AOE): superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in the blood of women with endometrial hyperplasia. Our results indicate that hyperplasia induces perturbance in oxidative balance, particularly in glutathione redox cycle enzymes

Citotoksično dejstvo crvenog vina na tumorske ćelije u in vitro uslovima

Benefitni efekat crvenog vina na zdravlje ljudi od davnina je poznat. Među alkoholnim pićima crveno vino pokazuje najjači efekat protiv pojave oboljenja povezanih sa oksidativnim stresom, kao što su kardiovaskularna, neurodegenerativna oboljenja, dijabetes i kancer.1 U okviru ove studije ispitan je citotoksični efekat crvenog vina sorte merlo (komercijalno dostupno vino i vina dobijena od klonova VCR1 i VCR101) poreklom iz Crne Gore, berba 2011, u odnosu na ćelijsku liniju kancera pankreasa (PANC-1) i ćelijsku liniju melanoma (A375). Citotoksični efekat vina je određen SRB metodom kroz praćenje ćelijskog preživljavanja kancerskih ćelija 48 sati nakon tretmana sa tri različita zapreminska procenta analiziranih vina (5, 10 i 20%). Dobijeni rezultati su pokazali citotoksični efekat svih analiziranih vina na obe ćelijske linije. Ćelijsko preživljavanje nakon tretmana vinima se kretalo od 36 do 64%. Citotoksični efekat svih vina u odnosu na A375 ćelije je bio veći nego na PANC-1 ćelijsku liniju, što je od posebnog značaja ako se uzme u obzir rezistentnost melanomskih ćelija na postojeće terapeutske tretmane. Takođe, klonska sortna vina su pokazala veći citotoksični efekat na A375 ćelijsku liniju od komercijalno dostupnog vina. Dobijeni rezultati su ukazali da umereno konzumiranje crvenog vina sorte merlo sa specifičnim geografskim poreklom predstavlja dobar izvor bioaktivnih komponenata sa pozitivnim biološkim efektom, što je od posebne važnosti za klonska sortna vina.3. kongres biologa Srbije : osnovna i primenjena istraživanja, metodika nastave, 21-25. septembar 2022., Zlatibor, Srbij

In vitro biological effects of clonal red wines

This study aimed to determine the phenolic compound content, in vitro antioxidative potential, and cytotoxic effects of four red wine samples: a commercial (V) and three clonal wines (V1, V2, and V3). LC/MS-MS, cyclic voltammetry, and MTT assay techniques were employed for this purpose. Results revealed that all wines were rich in phenolic compounds. Clonal wines outperformed the commercial ones in most phenolic compounds (except myricetin). Notably, V2 and V3 showed the highest levels of gallic acid, catechin, and epicatechin. Among them, V3 exhibited superior antioxidative activity. The MTT assay demonstrated stronger cytotoxic effects of the wine samples on pancreas (Bx-PC3) and colon (HT29) carcinoma cells (47% to 16% and 27% to 7% compared to control, respectively) than on the normal lung fibroblasts (MRC-5) cell line (106% to 77%). It can be concluded that HT29 cells were more sensitive than Bx-PC3 cells. Finally, both clonal and commercial wines serve as valuable sources of polyphenolic compounds, which could have a significant role in preventing cancer and diseases related to oxidative stress.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, 28-29 September 2023, Kragujevac, Serbi

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

THE USE OF INTEGRATIVE MULTI-OMICS APPROACH IN CULTIVATION AND CHARACTERIZATION OF GUT BACTERIA RELATED TO MICROBIOTA-GUT-BRAIN AXIS AS A SOURCE FOR NEXT GENERATION PROBIOTICS

There has been an epidemic of various non-communicable degenerative and autoimmune diseases, strongly associated with the modern lifestyle. Among them, neurodegenerative and psychiatric disorders represent a huge burden on society. Recently, all these diseases have been associated with the gut microbiota dysbiosis. Gut microbiota-host interaction research has been greatly improved due to development of molecular high-throughput techniques based on various ‘omics’ techniques coupled with bioinformatics and data science developments. However, the mechanisms of the host–microbiota crosstalk are still poorly understood. The NextGenBiotics project proposes an innovative integrative multi-omics research strategy for deciphering the mechanism behind the cross-talk among microbiota and gut-brain-axis. The 118 novel NGPs candidates belonging to Dorea sp., Blautia sp., Bacteroides sp., Roseburia sp., Sellimonas sp., Faecalicatena sp., Phascolarctobacterium faecium, and Faecalimonas sp. were cultivated. The 25 NGPs with confirmed safe status and potential probiotic potential were screened in C. elegans model for their effects on behavioural and neuronal activity. The most prominent candidates with ability to upregulate expression of genes involved in neurotransmiting are further tested in EAE (an animal model for MS) and CUMS depression model. The specific microbiota-derived metabolites have been identified as potential neuro- and psycho-biotics. The NextGenBiotics is highly ambitious project, dedicated to pioneering work in the field of multi-omics studies related to the cultivation of novel anaerobic NGPs and the studying of their effect on MGBA. This concept enabled studying bidirectional communication between gut microbiota and brain on the functional level that will significantly contribute to the growing body data related to MGBA. The results obtained during NextGenBiotics determined the genes/metabolites and the associated mechanisms involved in health-promoting effects of NGPs in MGBA beyond stateof- the-art, broadening the scientific knowledge and opening up the possible novel therapeutic approaches in prevention and therapy of neurodegenerative and psychiatric diseases.Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbi

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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature

Phenolic Composition and Cytotoxic Activity of Red Wine

Positive effects of moderate wine consumption in individuals with cardiovascular disease, hypertension, diabetes, and cancers have been shown in numerous epidemiological and clinical studies. This research examined the phenolic content of commercial and two clonal Merlot wines as well as their biological potential. The obtained results indicated that all analyzed samples were a good source of phenolic compounds. Cytotoxicity assay on melanoma (A375) and cervical (HeLa) cancer cell lines have shown that all analyzed wines inhibited the growth of human cancer cells in vitro with differing susceptibility among tested cell lines. Clonal wines in the volume ratio of 10 and 20% showed to be more efficient anti-proliferative agents than commercial wine regarding the A375 cells. This could be connected with higher total phenolic content in clonal wines. The effect of all analyzed samples on the A375 cells was greater compared to HeLa cell line.XVI International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, Belgrad