Copper (II) increases anti-Proliferative activity of thymoquinone in colon cancer cells by increasing genotoxic, apoptotic, and reactive oxygen species generating effects.

Thymoquinone is the main active compound derived from the essential oil of the Nigella sativa plant seed. While thymoquinone is an antioxidant, it has been reported in several studies that thymoquinone has dose-dependent pro-oxidant activity with the Fenton reaction in the presence of transition elements such as iron and copper. This study aimed to investigate cytotoxic, apoptotic, genotoxic, and reactive oxygen species (ROS) generating effects of thymoquinone treated with copper in colon cancer cells. HT-29 cells were treated with pro-oxidant-acting doses of thymoquinone alone and together with the non-toxic dose of Copper (II) Sulfate for 24 h. Cytotoxic, apoptotic, genotoxic, and ROS production activities were analyzed by MTT viability test, Acridine Orange/Ethidium Bromide (AO/EB) staining, alkaline single cell gel electrophoresis and H2DCF-DA assay, respectively. Viability results showed that thymoquinone and copper synergistically affect cancer cells, and DNA damage was increased with the synergic effect. The intracellular ROS was increased when thymoquinone and copper were applied together. Applying redox-active copper (II) with thymoquinone increases DNA damage, apoptosis, and cell death by increasing the amount of intracellular ROS through pro-oxidant activity. Treatments targeting copper-related pathways may open new therapeutic avenues for cancer treatment.

Mass spectrometry-based untargeted metabolomics study of non-obese individuals with non-alcoholic fatty liver disease.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of excessive fat in the liver, which can lead to fibrosis and has an increasing prevalence. NAFLD requires non-invasive diagnostic biomarkers. While typically observed in overweight individuals, it can also occur in non-obese/non-overweight individuals. Comparative studies on non-obese NAFLD patients are scarce. This study aimed to conduct a using liquid chromatography-high resolution mass spectrometry (LC-MS/MS)-based metabolic profiling of non-obese NAFLD patients and healthy controls. MATERIALS AND METHODS: The patient group consisted of 27 individuals with NAFLD, while the healthy control group included 39 individuals. Both groups were between 18 and 40 years old, had a BMI of less than 25 and had alcohol consumption less than 20 g/week for men and 10 g/week for women. Serum samples were collected and analyzed using LC-MS/MS. The data were analyzed using the TidyMass and MetaboAnalyst. RESULTS: The LC-MS/MS analyses detected significant changes in D-amino acid metabolism, vitamin B6 metabolism, apoptosis, mTOR signaling pathway, lysine degradation, and phenylalanine metabolism pathways in non-obese NAFLD patients. Significant changes were also observed in the metabolites D-pantothenic acid, hypoxanthine, citric acid, citramalic acid, L-phenylalanine, glutamine, and histamine-trifluoromethyl-toluidide, ß-hydroxymyristic acid, DL-Lactic acid, and 3-methyl-2-oxopentanoic. Overall, the study provides valuable insights into the metabolic changes associated with non-obese NAFLD patients and can contribute to the development of non-invasive diagnostic biomarkers for NAFLD. CONCLUSIONS: This study sheds light on the metabolic changes in non-obese NAFLD patients. Further research is needed to better understand the metabolic changes associated with NAFLD and to develop effective treatment options.

Investigation of serum enzyme activities and oxidative stress markers in preeclampsia: a multiparameter analysis.

OBJECTIVES: Preeclampsia, a high cause of fetomaternal morbidity-mortality, remains a significant burden affecting 8% of all pregnancies. Environmental conditions induce disease development leading to endothelial dysfunction in genetically predisposed women. Our aim is to discuss oxidative stress as a well-established contributing factor to disease progression with being the first study to show new evidence about serum dehydrogenase enzyme levels (isocitrate, malate, glutamate dehydrogenase) with oxidative markers (myeloperoxidase, total antioxidant-oxidant status, oxidative stress index). MATERIAL AND METHODS: Serum parameters were analyzed with photometric method (Abbott ARCHITECT c8000). RESULTS: The enzyme levels and oxidative markers were significantly higher in patients, supporting the redox imbalance in preeclampsia. According to ROC analysis, malate dehydrogenase showed an outstanding diagnostic ability with the highest AUC value of 0.9 and the cut-off value of 51.2 IU/L. Discriminant analysis including malate, isocitrate and glutamate dehydrogenase had predicted preeclampsia with an overall 87.9% accuracy. CONCLUSIONS: Considering the above results, we propose that the enzyme levels increase with oxidative stress functioning as antioxidant defense factors. The unique finding of the study is that the serum levels of malate, isocitrate and glutamate dehydrogenase can be used both separately and combined in the early prediction of preeclampsia. As a novel approach, we also offer combining serum isocitrate and glutamate dehydrogenase levels with ALT, AST tests to state liver functions more reliably in patients. Still, larger sample-sized studies investigating enzyme expression levels are required to confirm the recent findings and to reveal underlying mechanisms.

Maternal Serum Levels of Zinc, Copper, and Thiols in Preeclampsia Patients: a Case-Control Study.

Preeclampsia is one of the leading causes of maternal mortality-morbidity, and environmental factors act as the main driving force for the development of disease in genetically lean women. Trace element levels (zinc, copper) and thiol state (total, native thiol) may affect involved risk factors and play a role in the pathogenesis. The objective of our study is to assess trace element and thiol levels in patient and control groups. A total number of 88 pregnant women (in their third trimester) included 43 preeclampsia patients and 45 normotensive pregnant women as controls. The main findings of this study were the significantly elevated copper levels and decreased thiol levels (native and total thiols) in the patient group compared to controls (p < 0.05). Disulfide levels were not statistically different between the groups (p > 0.05). In patients, the predictive cutoff value of copper was 224 µg/dL and was 1.19 for the copper/native thiol ratio. Zinc levels were not statistically different between the two groups. Correlation analysis revealed no relationship between zinc-copper and zinc-total thiol levels in patients, while a positive correlation was evident in controls (zinc-copper, p < 0.05, r = 0.425, and zinc-total thiol levels, p < 0.05, r = 0.642). Patients had marginally high ALT and AST values in the normal range, and a significant difference was found between the two groups (p < 0.05). According to these results, elevated copper levels and decreased thiol levels may have a value for early prediction. The mechanisms that may be responsible for the altered element and thiol status have been discussed here in the context of oxidative stress.

Oxidative stress and schizophrenia: A comparative cross-sectional study of multiple oxidative markers in patients and their first-degree relatives.

OBJECTIVE: Schizophrenia (SCZ) is a chronic, disruptive mental disorder with unknown pathogenic mechanisms. Several studies evidenced that oxidative stress (OS) may be one of the causal factors to play a role in the pathophysiology of the disease. Our study aims to contribute to the SCZ research by investigating a possible relationship between the severity of illness (scored with "The Positive and Negative Syndrome Scale [PANSS]") and OS biomarkers in patients. We additionally assess the "first-degree-relatives (FDRs)" oxidative status with multiple parameters to test the idea of oxidative imbalance leads to disease progression as a genetical susceptibility factor. METHODS: This study included: 50 adult patients with SCZ, 50 unaffected FDRs, and 50 controls. OS biomarkers included myeloperoxidase (MPO), total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT). Photometric methods were used to measure the parameters in the peripheral blood samples of participants. Disulphide (DS) and oxidative stress index (OSI) parameters were calculated. RESULTS: TOS, DS, OSI levels were significantly higher, and TAS, TT, NT levels were significantly lower in both SCZ and FDRs than controls. In the SCZ group, MPO activity was significantly higher compared with other groups. Results in this study did not provide a strong correlation between the PANSS and selected biomarkers. There was a slightly negative correlation between TT and PANSS in the SCZ group (P = .041, r = -.297). CONCLUSION: OS biomarkers increased significantly in the peripheral blood of SCZ patients compared with other groups indicates the presence of OS in the aetiology of the disease. Mid-levels of oxidative markers found in FDRs imply that unaffected first-degree relatives have an increased risk for turning up to the clinical presentation stage.