The bisphenol S contamination level observed in human follicular fluid affects the development of porcine oocytes.

Bisphenol S (BPS), the main replacement for bisphenol A (BPA), is thought to be toxic, but limited information is available on the effects of Bisphenol S on ovarian follicles. In our study, we demonstrated the presence of Bisphenol S in the follicular fluid of women at a concentration of 22.4 nM. The effect of such concentrations of Bisphenol S on oocyte maturation and subsequent embryo development is still unknown. Therefore, we focused on the effect of Bisphenol S on in vitro oocyte maturation, fertilization, and embryo development. As a model, we used porcine oocytes, which show many physiological similarities to human oocytes. Oocytes were exposed to Bisphenol S concentrations similar to those detected in female patients in the ART clinic. We found a decreased ability of oocytes to successfully complete meiotic maturation. Mature oocytes showed an increased frequency of meiotic spindle abnormalities and chromosome misalignment. Alarming associations of oocyte Bisphenol S exposure with the occurrence of aneuploidy and changes in the distribution of mitochondria and mitochondrial proteins were demonstrated for the first time. However, the number and quality of blastocysts derived from oocytes that successfully completed meiotic maturation under the influence of Bisphenol S was not affected.

Effect of glucagon-like peptide-1 analogue liraglutide on primary cultures of rat hepatocytes isolated from lean and steatotic livers.

Non-alcoholic fatty liver disease and its complications are frequent causes of liver-related morbidity and mortality. Incretin glucagon-like peptide-1 (GLP-1) affects liver functions and metabolism. Although GLP-1 analogues are widely used in clinical practice, information regarding their potential toxic effect on hepatocytes in vitro is missing. Therefore, we evaluated the effect of GLP-1 analogue liraglutide on activity of caspases 3/7, cell viability and oxidative stress in primary cultures of hepatocytes. Primary cultures isolated from male Wistar rats fed a standard (ST1-group, 10% energy from fat) or a high-fat diet (HF-group, 71% fat) for 10 weeks were incubated with liraglutide (0.1-1000 nmol/l) for 24 h. Activities of caspases 3/7 and cellular dehydrogenases (WST-1), lactate dehydrogenase (LDH) leakage and oxidative stress (malondialdehyde concentration and DCFDA assay) were evaluated. HF-groups vs. ST1-groups showed higher caspases activity, LDH leakage and MDA production (p < 0.001) and lower cellular dehydrogenases activity (p < 0.01). Liraglutide induced a dose-dependent decrease of caspases activity in both groups, reduction of oxidative stress in HF-animals and exerted no negative effects on other parameters. In conclusion, GLP-1 analogue liraglutide decreased activity of caspases 3/7, reduced ROS production and didn't exhibit negative effects on cell viability and oxidative stress in primary cultures of hepatocytes isolated from lean and steatotic livers.

Biological Markers of Oxidative Stress in Cardiovascular Diseases: After so Many Studies, What do We Know?

Numerous conditions, including cancer, diabetes, aging, and atherosclerosis, are thought to be associated with oxidative stress. Oxidative stress is defined as a persistent imbalance between oxidation and antioxidation, resulting in the damage of cellular macromolecules and is often considered to be involved in wide variety of human diseases. However, the current literature is very heterogeneous making it rather difficult to draw general conclusions. Often, different biomarkers have been used in different health problems. In addition, individual biomarkers are often measured using nonspecific methods. The development of informative and highly reliable markers is very important. The conflicting results of numerous studies, including clinical trials, make it clear that despite the explosion of studies performed in the last decades, leading to nutritional guidelines recommending consumption of food-related antioxidants, direct proof is still lacking.

[Annual monitoring of side effects of administering sitagliptin in patients with type 2 diabetes mellitus]. / Rocní sledování vedlejsích úcinku podávání sitagliptinu u pacientu s diabetes mellitus 2. typu.

UNLABELLED: We present the results of an independent, drug company-unsupported follow-up of patients with type 2 diabetes mellitus (T2DM) treated with the dipeptidyl peptidase 4 inhibitor sitagliptin. 29 patients (16 men, 13 women) used sitagliptin 100 mg daily for one year as an add-on to their chronic antidiabetic therapy. 16 type diabetic patients formed a control group - they used their chronic antidiabetic therapy without sitagliptin. 10 additional patients (6 men and 4 women) were enrolled in the study and treated with sitagliptin for one month. Body weight, BMI, glycaemia, glycated hemoglobin (HbA1c), cholesterolemia, triacylglycerolemia and serum amylases were determined and abdominal ultrasonography was performed. Because significant changes in immunological tests had been found especially after one month of treatment, 10 additional patients (6 men and 4 women) were enrolled in the study and treated with sitagliptin for one month. Sitagliptin treatment led to a significant body weight loss of 1 kg per year. In the control group, no significant change was observed. Similar results were noticed in HbA1c level and fasting glycaemia - mild but statisticaly significant reduction in the sitagliptin group both after one month and one year (not in HbA1c), no difference in the control group. There was no change in cholesterolemia, or in triacylglycerolemia. In 33% of patients in the sitagliptin group, the level of liver steatosis decreased by ultrasonographic evaluation. This was not found in any of the patients case in the control group. The serum amylase levels increased slightly over the upper limit in two sitagliptin treated patients. In the other sitagliptin treated patients serum amylase remained within the laboratory limits, but slight, statistically significant elevation of serum amylases was observed in the intervened group. This result was not found in the control group. There were not differences in the frequency between occurence of mild respiratory infections in the sitagliptin and control group. Marginally significant decrease was observed in the intervened group. KEY WORDS: sitagliptin - type 2 diabetes mellitus - side effects.