Pitavastatin induces caspase-mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line.

Pitavastatin (PITA) is a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti-cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5-200 µM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h. Cell apoptosis and cell cycle analyses were performed in flow cytometry (0.1-100 µM). The evaluation of genotoxic effects and oxidative DNA damage of PITA (2-200 µM) were performed with standard comet assay, formamidopyrimidine glycosylase (fpg)-modified comet assay, and reactive oxygen species (ROS) activation in HeLa cells. PITA alone reduced cell viability in a dose-dependent manner (20-200, 20-200, and 5-200 µM for 24, 48, and 72 h, respectively, in MTT). The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly at 100 µM for 4 h and 20 µM for 24 h, respectively. PITA-induced apoptosis, an increased proportion of sub G1 cells, was monitored, and also, it increased the expression of active caspase-9 and caspase-3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) by western blotting and caspase 3/8/9 multiple assay kit. We conclude that PITA can be used to efficiently cervical cancer studies, and promising findings have been obtained for further studies.

Comprehensive estrogenic/anti-estrogenic, anticancer, mutagenic/anti-mutagenic, and genotoxic/anti-genotoxic activity studies on chemically characterized black poplar and Eurasian aspen propolis types.

Propolis is mainly composed of plant resins, and its type is named according to the primary plant origin in its composition. Identification of propolis botanical origin is essential for predicting and repeating its pharmacological activity because of the variations in chemical composition. This study aimed to compare chemical composition of black poplar (Populus nigra L.) type-propolis (PR1 and PR2) and Eurasian aspen (P. tremula L.)-type propolis (PR3) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique and to evaluate their biological activity profiles. According to LC-MS/MS results, in addition to marked caffeic acid phenethyl ester content in PR1 and PR2, flavonoid aglycones such as pinocembrin, chrysin, pinobanksin, and galangin were found to be dominant in these samples. On the other hand, PR3 contained relatively high concentrations of phenolic acids such as ferulic acid, p-coumaric acid, and trans-cinnamic acid. The anti-estrogenic activity test showed that PR2 exerted the highest anti-estrogenic activity by inhibiting cell proliferation by 44.6%. All propolis extracts showed anticancer activity, which was justified by decreasing activity on the 3D spheroid size in a concentration-dependent manner. Besides, all extracts showed moderate or potent antimutagenic activity in Salmonella typhimurium TA98 and TA100 strains with and without metabolic activation, respectively. In addition, the Comet assay results revealed that propolis extracts have a geno-protective effect against H2O2-induced DNA damage in CHO-K1 cells at 0.625 and 1.25 µg/mL concentrations. Overall, the result of this study may help in preparing standardized propolis extracts and developing products with defined pharmacological benefits in the food supplements industry.

Evaluation of oxidative stress and immune parameters of boron exposed males and females.

There is growing evidence that boron (B) and B compounds are essential nutrients for animals and humans. Besides, B compounds have been suggested to treat inflammation and oxidative stress. As a part of our "Boron Project II" on B-exposed persons in Bandirma and Bigadic (Turkey) between 2014 and 2017, anti-oxidant/pro-oxidant and inflammatory parameters were assessed. In this first large-scale human study biomarkers of oxidative stress such as the enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and the levels of malondialdehyde (MDA), glutathione (GSH) and 8-hydroxy-2'-deoxy-guanosine (8-OH-dG) were investigated, in relation to B exposure. The immune biomarkers interleukin (IL)-1ra, IL-6, IL-8 and nuclear factor kappa B (NF-κB) levels were included. There was no influence of human exposure to B on the parameters of oxidative stress and inflammation.

Oxidative stress status of Turkish welders.

Welding, a fabrication process that joins metals or thermoplastics by causing coalescence, is indispensable in modern society and ubiquitous in industry. Welding generates fumes that contain several metals and gases that comprise fine and ultrafine particles with the potential for adverse effects. Although health risks of welders have been evaluated in different populations, occupational exposure to welding fumes is still considered to be an important health problem, especially in developing countries. The aim of this study was to investigate the effects of welding fume exposure on important oxidative stress parameters such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), total glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in Turkish welders (n = 48). The influence of confounding factors such as age, smoking habits, alcohol consumption, and duration of exposure on the studied parameters was also analyzed. In our study, significant decreases in the levels of GSH and activities of CAT, SOD, and GPx and significant increases of MDA, 8-OHdG levels and GR activity were found in the workers compared to the controls. There was a negative correlation between GSH levels and alcohol usage. Also, older workers (≥35 years) had significantly higher GR levels than younger workers. But smoking and alcohol usage, duration of exposure, and utilization of protective measures had no significant effect on the studied parameters in the workers. These results indicate that occupational exposure to welding fumes appears to induce oxidative stress and oxidative DNA damage.

Effects of phytochemicals against diabetes.

Diabetes mellitus, a chronic metabolic disease, characterized by elevated levels of blood glucose and insufficiency in production and action of insulin is the seventh leading cause of death worldwide. Numerous studies have shown that diabetes mellitus is associated with increased formation of free radicals and decrease in antioxidant potential. In the patients with diabetes mellitus, the levels of antioxidant parameters are found to decrease, hence in many studies phytochemicals which can exert antioxidant and free radical scavenging activities, are suggested to improve the insulin sensitivity. Several phytoactive compounds such as flavonoids, lignans, prophenylphenols, are also found to combat the complications of diabetes. This chapter mainly focuses on the relationship between diabetes mellitus and preventive roles of various phytochemicals on diabetes via their antioxidant properties.