Mechanisms of cell death induced by hexabromocyclododecane (HBCD) involves apoptosis, autophagy, and ER stress.

Hexabromocyclododecane (HBCD), was a widely utilized brominated flame retardant, commonly found in a wide range of household products. The pervasiveness of HBCD has identified the presence of this chemical in foods and in human tissues. Therefore, HBCD has been identified as a chemical of concern. The aim was to investigate the degree of cytotoxicity of HBCD in a range of cell lines derived from different tissues, (including hematopoietic, nerve, liver, and kidney-derived cells) with a view of determining any differential cell type effects. In addition, this study also investigated the mechanism(s) by which HBCD could cause cell death. The results showed that HCBD was considerably more toxic to leukocyte-derived (RBL2H3) and neuronal-derived (SHSY-5Y) cells with LC50 values of 1.5 and 6.1 µM, respectively, compared to cells derived from liver (HepG2) and kidney (Cos-7), which had LC50 values of 28.5 and 17.5 µM, respectively. A detailed investigation of the mechanism(s) of cell death showed that HBCD caused, at least in part, Ca2+ -dependent cell death, caspase-activated apoptosis, and autophagy, but there was little evidence for either necrosis or necroptosis occurring. Furthermore, it was shown that HBCD can also induce the ER stress response which is a known trigger of both apoptosis and autophagy and therefore this could be one of the crucial events by which cell death is initiated. As each of these cell death mechanisms was investigated in at least two different cell lines and no differences were identified, it is likely that the mode of action is not cell-type specific.

Comparing the efficiency of N-doped TiO2 and commercial TiO2 as photo catalysts for amoxicillin and ciprofloxacin photo-degradation under solar irradiation.

Advanced oxidation processes (AOPs) have gained traction as alternative solutions for eliminating pollutants from pharmaceutical wastewater for reuse. In this research, the performance of two photo-catalysts (Commercial TiO2 and synthesis N-doped TiO2) were compared in terms of the degradation of amoxicillin and ciprofloxacin from an aqueous solution using a photo-catalytic batch system under solar irradiation. The influence of five operating factors is: pH (5-11), H2O2 concentrations (200-600) mg/L, catalyst concentrations (25-100 mg/L), Antibiotic concentration (25-100) mg/L and reaction time (30-120 min), on the oxidation of the listed above pollutants were investigated using the central composite design (CCD) of response surface methodology (RSM). The catalyst of N-doping TiO2 was synthesized by sol-gel method, using the urea (CH4N2O) as a nitrogen source. The resulting material was analyzed using Scanning Electron Microscopy (SEM), X-Ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Additionally, it can be observed from the analysis of the characteristics of N-doped TiO2 the homogenous dispersion of nitrogen molecules, small particle sizes, and energy-gap reduction, prompting a 6% increase in antibiotic degradation compared with Com. TiO2. In the RSM analysis, the ideal conditions were found to be a pH of 5, H2O2 conc. of 400 mg/L, catalyst conc. of 50 mg, and antibiotics conc. of 25 mg/L for an antibiotics reduction rate of 89.31% (AMOX/Com. TiO2/Solar), 90.2 (CFX/Com. TiO2/Solar), 95.8% (AMOX/N-TiO2/Solar) and 97.3% (CFX/N-TiO2/Solar). Experimental results were in good agreement with predictions because the predicted R2 matched well with the adjusted R2.

Cytotoxicity by endocrine disruptors through effects on ER Ca2+ transporters, aberrations in Ca2+ signalling pathways and ER stress.

Concerns regarding man-made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti-estrogenic properties and some were also shown to bind to a variety of hormone receptors. However, since the 1990s it has also been identified that many of these EDC additionally, have the ability of causing abnormal alterations in Ca2+ signalling pathways (also commonly involved in hormone signalling), leading to exaggerated elevations in cytosolic [Ca2+] levels, that is known to cause activation of a number of cell death pathways. The major emphasis of this review is to present a personal perspective of the evidence for some types of EDC, specifically alkylphenols and brominated flame retardants (BFRs), causing direct effects on Ca2+ transporters (mainly the SERCA Ca2+ ATPases), culminating in acute cytotoxicity and cell death. Evidence is also presented to indicate that this Ca2+ATPase inhibition, which leads to abnormally elevated cytosolic [Ca2+], as well as a decreased luminal ER [Ca2+], which triggers the ER stress response, are both involved in acute cytotoxicity.

Regucalcin ameliorates doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria.

Doxorubicin (DOX) is a potent anticancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 h over a range of concentrations, and the LC50 was determined to be 7 µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 h, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically induced cell stress.