Biochemical metal accumulation effects and metalloprotein metal detoxification in environmentally exposed tropical Perna perna mussels.

Marine bivalves have been widely applied as environmental contamination bioindicators, although studies concerning tropical species are less available compared to temperate climate species. Assessments regarding Perna perna mytilid mussels, in particular, are scarce, even though this is an extremely important species in economic terms in tropical countries, such as Brazil. To this end, Perna perna mytilids were sampled from two tropical bays in Southeastern Brazil, one anthropogenically impacted and one previously considered a reference site for metal contamination. Gill metallothionein (MT), reduced glutathione (GSH), carboxylesterase (CarbE) and lipid peroxidation (LPO) were determined by UV-vis spectrophotometry, and metal and metalloid contents were determined by inductively coupled plasma mass spectrometry (ICP-MS). Metalloprotein metal detoxification routes in heat-stable cellular gill fractions were assessed by size exclusion high performance chromatography (SEC-HPLC) coupled to an ICP-MS. Several associations between metals and oxidative stress endpoints were observed at all four sampling sites through a Principal Component Analysis. As, Cd, Ni and Se contents, in particular, seem to directly affect CarbE activity. MT is implicated in playing a dual role in both metal detoxification and radical oxygen species scavenging. Differential SEC-HPLC-ICP-MS metal-binding profiles, and, thus, detoxification mechanisms, were observed, with probable As-, Cu- and Ni-GSH complexation and binding to low molecular weight proteins. Perna perna mussels were proven adequate tropical bioindicators, and further monitoring efforts are recommended, due to lack of data regarding biochemical metal effects in tropical species. Integrated assessments, as performed herein demonstrate, are invaluable in evaluating contaminated aquatic environments, resulting in more accurate ecological risk assessments.

Role of Sonic hedgehog signaling in cell cycle, oxidative stress, and autophagy of temozolomide resistant glioblastoma.

The first-line chemotherapy treatment for Glioblastoma (GBM) - the most aggressive and frequent brain tumor - is temozolomide (TMZ). The Sonic hedgehog (SHH) pathway is involved with GBM tumorigenesis and TMZ chemoresistance. The role of SHH pathway inhibition in the potentiation of TMZ's effects using T98G, U251, and GBM11 cell lines is investigated herein. The combination of GANT-61 and TMZ over 72 hr suggested a synergistic effect. All TMZ-resistant cell lines displayed a significant decrease in cell viability, increased DNA fragmentation and loss of membrane integrity. For T98G cells, G2 /M arrest was observed, while U251 cells presented a significant increase in reactive oxygen species production and catalase activity. All the cell lines presented acidic vesicles formation correlated to Beclin-1 overexpression. The combined treatment also enhanced GLI1 expression, indicating the presence of select resistant cells. The selective inhibition of the SHH pathway potentiated the cytotoxic effect of TMZ, thus becoming a promising in vitro strategy for GBM treatment.

Influence of water matrix components and peroxide sources on the transformation products and toxicity of tebuthiuron under UVC-based advanced oxidation processes.

Coupling of UV-C irradiation to different peroxides (H2O2, S2O82- and HSO5-) has great potential to degrade persistent organic compounds due to the formation of HO• or SO4•- species. However, an in-depth comparison between the performance of different UV-C/peroxide processes as a function of (i) target compound degradation, (ii) generated transformation products and (iii) lethal/sub lethal toxicity effects has not yet been performed. To this end a comparison study was carried out to evaluate the effectiveness of different UV-C/peroxide processes using the herbicide tebuthiuron (100 or 500 µg L-1) as a model pollutant. TBH degradation experiments were performed at lab-scale in real municipal wastewater treatment plant effluent and distilled water. Faster degradation occurred by increasing peroxide concentration from 735 to 2206 µmol L-1 in the municipal wastewater treatment plant effluent, mainly for S2O82-. Experiments performed in the presence of peroxide trapping agents - HO• and SO4•- (methoxibenzene) or HO• (2-propanol) - revealed that oxidation in the UV-C/S2O82- system occurs mainly through SO4•-. Lower toxicity for the MWWTP effluent was obtained after oxidative treatments using hydrogen peroxide or monopersulfate as oxidants which react mainly through HO• radicals. Two mechanistic pathways were proposed for tebuthiuron degradation: (i) hydrogen abstraction by HO• (H2O2 and HSO5-) and (ii) electron transfer by SO4•- (S2O82-). In addition, one unprecedented transformation product was identified. In conclusion, results emphasize the relevance of comparing the degradation of toxic compounds in the presence of different peroxide sources and matrices and simultaneouly evaluating responses chemical and biological endpoints.