Some pleiotropic effects of statins on hepatocellular carcinoma cells: Comparative study on atorvastatin, rosuvastatin and simvastatin.

PURPOSE: For many years, statins have been the most commonly used drugs in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and rosuvastatin at different concentrations on hepatocellular carcinoma (HepG2) cells. MATERIALS AND METHODS: The MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein diacetate (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay. RESULTS: The obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin. CONCLUSION: The less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.

Urban Air Pollution Associated with the Incidence of Autoimmune Thyroid Diseases.

Background: Endocrine disrupting air pollutants such as sulphur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), fine particle matter (PM2.5), and ozone (O3) can affect thyroid gland function on the level of synthesis, metabolism, and the action of its hormones. Objective: The aim of this study was to establish whether increased air pollution could contribute to an increased incidence of autoimmune thyroid diseases (AITD). Methods: A retrospective analysis was conducted of the medical records of 82000 patients at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. The target group of this study comprised a total of 174 patients from the Lukavac area. Daily data on concentrations of air pollutants were collected from the air quality monitoring station located in Lukavac. The study covered the period from 2015 to 2020. Results: The results of the monitoring confirmed the presence of air pollutants in concentrations above the permitted limits throughout the entire observed period. Concentrations of PM2.5, SO2, NO2, CO, and O3 were in the range of 1.90-431.40 µg/m3, 3.60-620.50 µg/m3, 3.40-66.20 µg/m3, 48.00-7002.00 µg/m3, and 0.70-89.40 µg/m3, with means of 64.08 µg/m3, 77.48 µg/m3, 22.57 µg/m3, 1657.15 µg/m3, and 31.49 µg/m3, respectively. During the six-year period, 174 cases of AITD were registered, of which 150 (86.21%) were women and 24 (13.79%) men. Hashimoto's thyroiditis was found in 33 patients (18.97%), whilst 141 patients (81.03%) were diagnosed with atrophic thyroiditis. The highest total incidence of autoimmune thyroiditis was recorded in 2017, when it reached 99.49, 95% CI. Conclusion: The effects of chronic exposure to a mixture of air pollutants on the function of the thyroid gland are still not sufficiently well-known, but the numerical tendency towards a higher incidence of AITD in this study, albeit without statistical significance (p>0.05), still underlines the need for additional research.

Deterministic and probabilistic human health risk assessment for fluorides in drinking groundwater from Lukavac, Bosnia and Herzegovina.

Although fluorides are essential for dental health, there are growing health concerns regarding the risk-benefit ratio of fluoride exposure. The objectives of the study were to obtain data on the amount and human health risks of fluoride in drinking groundwater, as well as to compare and evaluate the differences in the outputs obtained by two different approaches in health risk assessment (deterministic vs probabilistic). From a densely populated industrial area of north-eastern Bosnia and Herzegovina, a total of 54 groundwater samples were collected. Fluoride concentrations varied from 1.69 to 3.52 mg/L. The WHOapos;s threshold value for fluoride in drinking water was exceeded in all the samples analysed, indicating an increased daily intake of fluoride from groundwater. Deterministic and semi-probabilistic techniques were used for exposure assessment and health risk quantification. Generally, the deterministic approach resulted in acceptable health risks in most adult exposure scenarios. However, the Monte Carlo simulation revealed that 20.6, 20.8, and 99.8% of adult males, females, and children, respectively, were above the tolerable upper intake level, indicating that both adults and children face a significant health risk. Nevertheless, small children are more vulnerable to environmental hazards than youth and adults. Hence, a more in-depth risk-benefit analysis is required to reduce/or optimize fluoride content in drinking water to prevent tooth decay and fluorosis at all ages. Considering that optimal daily intake of fluorides is a crucial factor for preserving human health, decision-makers should take steps to emphasize the importance of continuous monitoring of fluoride concentrations in drinking water.

Human health risk assessment of lead, cadmium, and mercury co-exposure from agricultural soils in the Tuzla Canton (Bosnia and Herzegovina).

The aim of this study was to assess the risk of human exposure to lead (Pb), cadmium (Cd), and mercury (Hg) through agricultural soil by considering both uncertainty and variability in key exposure parameters. For this reason we collected soil samples from 29 locations in the Tuzla Canton (Bosnia and Herzegovina) and measured their metal levels with inductively coupled plasma atomic emission or absorption spectrometry (ICP-AES and ICP-AAS, respectively). The levels of Pb ranged from 13.33 to 1692.33 mg/kg, of Cd from 0.05 to 3.67 mg/kg, and of Hg from 0.02 to 2.73 mg/kg. To estimate cancer and non-cancer risks we used deterministic and semi-probabilistic methods. Lead was found to involve higher health risk than the other two heavy metals. Its hazard index (HI) decreased between population groups (children>women>men) and exposure routes (ingestion>skin contact>inhalation). Our Monte Carlo simulations indicated that Pb HIs for both adult populations had a 0.6 % probability to exceed the threshold value of 1, while in children this probability was 14.2 %. Cd and Hg showed no probability to exceed the threshold in any scenario. Our simulation results raise concern about possible adverse health effects of heavy metals from soil, especially in children. It is very important to continue monitoring environmental pollution and assess human health risk, not only with respect to soil, but also with other important environmental compartments, such as air and water.

The Epidemiological Characteristics of Autoimmune Thyroiditis in the Tuzla Canton in the Period from 2015 to 2020.

BACKGROUND: Bosnia and Herzegovina (B&H) is one of the countries of Southeast Europe with the lack of data about chronic autoimmune thyroid diseases (CAITD) epidemiology. OBJECTIVE: This research aimed to assess incidence of CAITD in the Tuzla Canton of B&H during a 6-year period (2015-2020). METHODS: We retrospectively evaluated 82,000 hospital records of inpatients and outpatients with possible thyroid symptoms residing in Tuzla Canton of B&H (total of 445,028 inhabitants). The study included patients with laboratory and clinical proof of autoimmune thyroid diseases (AITD). Incidence rates were calculated with age standardisation using European standard population. Trends in incidence were evaluated as moving three-year averages. RESULTS: During the observed period, 1875 patients satisfied the diagnostic criteria for CAITD with male to female ratio of 1: 8.01. Median age of all cases was 46 years (interquartile range: 31 to 61) and women and men were on average the same age at the time of diagnosis. The overall standardized incidence was found to be 71.25 per 105 (%95 CI=63.36-79.15). The overall standardized incidence in men was 16.25 per 105 and 123.74 per 105 in women. In the end of the observed period, AITD prevalence was 427.52 per 105 (% 95 CI=408.17-446.87). CONCLUSION: There was a slight decline of incidence in our region during the observed period. This decrease might be the result of combination of various factors, mainly the Corona epidemics outbreak and emigration. On the basis of the lower incidence rate in the Tuzla Canton, one can assume that iodine prophylaxis carried out in order to eradicate goitre had satisfied expectations because there had not been any enormous increase in patients with AITD.