Assessment of the cytotoxic, genotoxic, and apoptotic potential of flurbiprofen in HeLa and HepG2 cell lines.

In the literature, the anticancer potential of flurbiprofen isn't fully understood. In this study, the cytotoxic, genotoxic, and apoptotic effects of flurbiprofen were evaluated in human cervical and liver cancer cells. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and it was observed that cytotoxicity increased in a concentration- and time-dependent manner. Genotoxicity was determined using alkaline Comet assay. DNA damage increased in a concentration-dependent manner. Early apoptosis was evaluated using real-time polymerase chain reaction, and it was found that apoptotic gene levels increased while antiapoptotic gene levels decreased. Late apoptosis and cell cycle analyzes were determined using flow cytometry. No evidence of late apoptosis was observed, and no significant arrest was found in the cell cycle. In conclusion, it seems that flurbiprofen has a cytotoxic, genotoxic, and apoptotic effects in both human cancer cell lines. Moreover, the findings indicate that flurbiprofen is effective at the gene level and induces apoptosis with an intracellular pathway.

Evaluation of the Methylation and Acetylation Profiles of Dinitroaniline Herbicides and Resveratrol on the V79 Cell Line.

OBJECTIVES: Herbicides are among the most widely used pesticide compounds for plant growth control worldwide. Risk assessment of the dinitroaniline-derived herbicides pendimethalin and trifluralin is important for foodborne or other means of exposure. In this study, we aimed to evaluate the methylation and acetylation profiles of pendimethalin and trifluralin, which we have high levels of exposure to in various ways. Furthermore, we also determined the protective effect of resveratrol, an antioxidant compound, against the possible toxic effects of these pesticides. MATERIALS AND METHODS: The effects of pendimethalin and trifluralin alone (25, 50, 100 µM) and in combination with resveratrol (100 µM) on DNA methyltransferase (DNMT1) 1, 3a, and 3b; and histone deacetylase (HDAC) 1 and HDAC3 gene expression were evaluated by real-time polymerase chain reaction. RESULTS: According to the results, pendimethalin caused a significant decrease in DNMT1, 3a, 3b and HDAC expressions at all concentrations, whereas HDAC1 and 3 expression was increased at the concentration of 25 µM, when applied together with resveratrol. There were no changes in DNMT1 or 3b expression levels. Unlike pendimethalin, trifluralin increased DNMT1 expression in a concentration-dependent manner. While DNMT3a and DNMT3b expression levels increased significantly, HDAC1 and 3 expression levels did not change significantly. The expression levels of HDAC1 and HDAC3 increased at all concentrations of trifluralin combination with resveratrol. Moreover, DNMT levels increased at the concentrations of 50 and 100 µM. CONCLUSION: Epigenetic gene expression results showed that pendimethalin and trifluralin might cause tissue function loss and chromosome damage as a result of direct effects on cell viability by causing expression level changes in all studied genes. It can also be concluded that the changes that occur in gene expression may induce tumor development. Further studies are needed to elucidate the possible toxicity mechanisms of these herbicides, considering the relationship between epigenetic changes and various diseases.

In vitro investigation of the effects of boron nitride nanotubes and curcumin on DNA damage.

BACKROUND: Stem cells provide an opportunity to analyse the effects of xenobiotic on cell viability, differentiation and cell functions. Evaluation of the possible cytotoxic and DNA damaging effects on bone marrow CD34+ stem cells is important for their ability to differentiate into blood cells, and also for bone marrow diseases therapy. Boron nitride nanotubes and curcumin are potential nanoformulation agents that can be used together in the treatment of cancer or bone marrow diseases. Therefore, it is important to evaluate their possible effects on different cell lines. OBJECTIVES: In this study, it was aimed to evaluate the cytotoxic and DNA damaging effects of boron nitride nanotubes which are commonly used in pyroelectric, piezoelectric and optical applications, but there is not enough information about its biocompatibility. Also, it was intended to research the effects of curcumin being used frequently in treatment processes for antioxidant properties. METHODS: The possible cytotoxic and DNA damaging effects of boron nitride nanotubes and curcumin on CD34+ cells, HeLa and V79 cells were evaluated by MTT assay and Comet assay, respectively. RESULTS AND CONCLUSION: Boron nitride nanotubes and curcumin had cytotoxic effects and cause DNA damage on CD34+ cells, HeLa and V79 cells at several concentrations, probably because of increased ROS level. However, there were not concentration - dependent effect and there were controversial toxicity results of the studied cell lines. Its mechanism needs to be enlightened by further analysis for potential targeted drug development. Graphical abstract.

Preventive role of Pycnogenol® against the hyperglycemia-induced oxidative stress and DNA damage in diabetic rats.

Diabetes mellitus, a complex progressive metabolic disorder, leads to some oxidative stress related complications. Pycnogenol® (PYC), a plant extract obtained from Pinus pinaster, has been suggested to be effective in many diseases including diabetes, cancer, inflammatory and immune system disorders. The mechanisms underlying the effects of PYC in diabetes need to be elucidated. The aim of this study was to determine the effects of PYC treatment (50 mg/kg/day, orally, for 28 days) on the DNA damage and biochemical changes in the blood, liver, and kidney tissues of experimental diabetic rats. Changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase enzymes, and the levels of 8-hydroxy-2'-deoxyguanosine, total glutathione, malondialdehyde, insulin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, high density lipoprotein, low density lipoprotein, total cholesterol, and triglyceride were evaluated. DNA damage was also determined in the whole blood cells and the liver and renal tissue cells using the alkaline comet assay. PYC treatment significantly ameliorated the oxidative stress, lipid profile, and liver function parameters as well as DNA damage in the hyperglycemic rats. The results show that PYC treatment might improve the hyperglycemia-induced biochemical and physiological changes in diabetes.

Protective Effects of Ursolic Acid in the Kidneys of Diabetic Rats.

OBJECTIVES: Diabetes, a heteregenous metabolic and chronic disease, is a growing health problem in most countries. It has been claimed that diabetes is associated with the increased formation of free radicals and decreased in antioxidant potential. Oxidative stress formed in diabetes may cause DNA damage in the tissues. Ursolic acid, a well-known pentacylic triterpene, is commonly used in traditional Chinese medicine due to its beneficial health effects such as antioxidant, anticancer, and antiulcer properties. The aim of this study was to investigate the effects of ursolic acid in the kidneys of Wistar albino rats with streptozotocin-induced diabetes. MATERIALS AND METHODS: DNA damage was evaluated in the kidney cells of rats using alkaline comet assays. Oxidative stress parameters such as CAT, SOD, GR, and GSH-Px enzyme activities and total GSH and MDA levels were also evaluated. RESULTS: Ursolic acid treatment was found to significantly decrease DNA damage, GR enzyme activities, and MDA levels, and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities in diabetic rats. CONCLUSION: According to our results, it seems that ursolic acid may be beneficial against diabetes-induced renal damage.

Effects of cinnamic acid on complications of diabetes

Background/aim: Diabetes mellitus (DM) is a major health problem worldwide. Cinnamic acid (CA) and its derivatives are synthesized in plants and increasing attention has been given to them in recent years due to the high number of beneficial health properties attributed to their consumption. The aim of this study was to investigate the effects of CA on streptozotocin-induced diabetes in Wistar albino rats. Materials and methods: DNA damage was evaluated in the blood, liver, and kidney cells of rats by the alkaline comet assay. Oxidative stress parameters such as catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase activities and 8-hydroxy-2-deoxyguanosine, total glutathione, and malondialdehyde levels; biochemical parameters including insulin, total bilirubin, and BCA protein levels; hepatic enzyme levels such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase; and lipid profile parameters including high-density lipoprotein, low-density lipoprotein, total cholesterol, and triglyceride levels were also evaluated. Results: DM caused genotoxic damage and alterations in lipid profiles, oxidative stress parameters, and hepatic enzymes levels. CA treatment ameliorated these effects. Conclusion: It seems that CA might have a role in the prevention of the complications of diabetes.

d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.

It is known that diabetes causes some complications including alterations in lipid profile, hepatic enzyme levels but also it causes oxidative stress. Limonene, a major component of Citrus oils, has important health beneficial effects in lowering the level of oxidative stress due to its antioxidant activity. The aim of this study was to investigate the effects of D-limonene on streptozotocin (STZ)-induced diabetes in Wistar albino rats. For this purpose, DNA damage was evaluated by alkaline comet assay. Changes in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), total glutathione (GSH), malondialdehyde (MDA), insulin, total bilirubin and BCA protein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglyceride were also evaluated. D-limonene treatment was found to significantly decrease DNA damage, GR enzyme activities and MDA levels and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. According to our results, it seems that D-limonene might have a role in the prevention of the complication of diabetes in rats.