EFFECTS OF NDL-PCB AND TCDD ON INTESTINAL EPITHELIAL CELLS HOMEOSTASIS

Polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD) are persistent organic pollutants (POPs) recognized as causing adverse effects on humans, animals and environment. Exposure occurs mainly through the consumption of contaminated food, in particular those of animal origin. the aim of the current study was to evaluate the effects of three ndl-PCB congeners, PCB 138, PCB 153 and PCB 180, and tetrachlorodibenzo-p-dioxins (TCDD), alone and differently combined, on non tumorigenic rat intestinal epithelial cell line (IEC-6). The results of the current study showed that ndl-PCBs and TCDD reduced significantly cell viability only at the highest concentrations (50-100 µM and 0.1-1 µM, respectively); such effect was not linked to apoptosis induction or cell cycle arrest. The contemporary presence of more than one contaminant (differently combined) did not induce any enhancement of effects on IEC-6 cell line. Intestinal restitution was not affected by low non cytotoxic concentrations of ndl-PCBs and TCDD. The results of the current study highlight the need to continue the evaluation of toxic properties of ndl-PCBs, which represent a less studied PBCs; such studies could provide useful information in particular in term of risk assessment

Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model

PURPOSE: Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly-methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs. METHODS: Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS-NPs (100 μg/mL) and then to SWs (0.43 mJ/mm(2) for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control. RESULTS: There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% ± 3.89%) and apoptotic (27.45% ± 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 (P<0.001) and a significant downregulation of TIGAR (P<0.05) and MAP3K5 (P<0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c (P<0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth. CONCLUSION: The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment’s efficacy in an in vitro neuroblastoma model