Polysaccharides from Phormidium versicolor (NCC466) protecting HepG2 human hepatocellular carcinoma cells and rat liver tissues from cadmium toxicity: Evidence from in vitro and in vivo tests

© 2018 Elsevier B.V. The in vitro antioxidant, cytotoxic and cytoprotective properties and in vivo hepatoprotective activities of crude polysaccharides extracted from cyanobacteria Phormidim versicolor NCC466 (CFv-PS) were investigated. The CFv-PS, identified as heteropolysaccharides with molecular weight of 63.79 kDa, exhibited relatively strong antioxidant activity, in a concentration-depended manner, in vitro assays. Additionally, CFv-PS did not induce cytotoxic effect on HepG2 human hepatocellular carcinoma cells within the range of tested concentrations (25–150 μg·mL−1) while preventing them against Cd. Moreover, in rats subjected to Cd-induced hepatotoxicity, CFv-PS pretreatment significantly (P < 0.05) reduced the level of ALAT, ASAT, biliburin, MDA, protein carbonyl and DNA damage, and markedly increased enzyme activities in liver tissues. These findings suggest that the cyanobacteria Phormidium versicolor is a potential source of natural products possessing antioxidant, cytoprotective and hepatoprotective properties

The global biopharma industry and the rise of Indian drug multinationals: implications for Australian generics policy

This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of 'big pharma' has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life cycle management techniques, including the launch of 'authorised generics'. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products

PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment during Genotoxic Stress in Human Cells

The function of BRCA1 in response to ionizing radiation, which directly generates DNA double strand breaks, has been extensively characterized. However previous investigations have produced conflicting data on mutagens that initially induce other classes of DNA adducts. Because of the fundamental and clinical importance of understanding BRCA1 function, we sought to rigorously evaluate the role of this tumor suppressor in response to diverse forms of genotoxic stress.We investigated BRCA1 stability and localization in various human cells treated with model mutagens that trigger different DNA damage signaling pathways. We established that, unlike ionizing radiation, either UVC or methylmethanesulfonate (MMS) (generating bulky DNA adducts or alkylated bases respectively) induces a transient downregulation of BRCA1 protein which is neither prevented nor enhanced by inhibition of PIKKs. Moreover, we found that the proteasome mediates early degradation of BRCA1, BARD1, BACH1, and Rad52 implying that critical components of the homologous recombination machinery need to be functionally abrogated as part of the early response to UV or MMS. Significantly, we found that inhibition of BRCA1/BARD1 downregulation is accompanied by the unscheduled recruitment of both proteins to chromatin along with Rad51. Consistently, treatment of cells with MMS engendered complete disassembly of Rad51 from pre-formed ionizing radiation-induced foci. Following the initial phase of BRCA1/BARD1 downregulation, we found that the recovery of these proteins in foci coincides with the formation of RPA and Rad51 foci. This indicates that homologous recombination is reactivated at later stage of the cellular response to MMS, most likely to repair DSBs generated by replication blocks.Taken together our results demonstrate that (i) the stabilities of BRCA1/BARD1 complexes are regulated in a mutagen-specific manner, and (ii) indicate the existence of mechanisms that may be required to prevent the simultaneous recruitment of conflicting signaling pathways to sites of DNA damage

Detoxification of rats subjected to nickel chloride by a biomaterial-based carbonated orthophosphate

International audienceSummary Recently, the therapeutic approaches of the detoxification against the metals (nickel) in the body are the use of biomaterials such as carbonated hydroxyapatite. The aim of this study is therefore to analyze the physiological and physicochemical parameters of strain white rats "Wistar" receiving nickel chloride and to study the protective associative of apatite against adverse effects of this metal, and this in comparison with control rats. Our results showed that the nickel induced in rats an oxidative stress objectified by elevated levels of thiobarbituric acid-reactive substances and conjugated dienes associated with inhibition of the activity of the antioxidant defense system such as glutathione peroxidase, superoxide dismutase and catalase in the liver, kidney, spleen and erythrocyte. Disorders balances of ferric, phosphocalcic, a renal failure and a liver toxicity were observed in rats exposed to nickel. As well as a significant increase in the rate of nickel in the bones and microcytic anemia was revealed. However, the implantation of carbonated hydroxyapatite in capsule form protects rats intoxicated by the nickel against the toxic effects of this metal by lowering the levels of markers of lipid peroxidation and improving the activities of defense enzymes. Our implantation technique is effective to correct ferric balance and phosphocalcic equilibrium, to protect liver and kidney function, to reduce the rate of bone nickel and to correct anemia. They clearly explain the beneficial and protective of our biomaterial which aims the detoxification of rats receiving nickel by substituting cationic (Ca2+ by Ni2+) and anionic (OH− by Cl−) confirmed by physicochemical characterization like the IR spectroscopy and X-ray diffraction. These techniques have shown on the one hand a duplication of OH− bands (IR) and on the other hand the increase of the volume of the apatite cell after these substitutions (X-ray diffraction)

Décomposition thermique de fluorapatites carbonatées sodées

Une série de fluorapatites carbonatées sodées de composition variable a été préparée par la méthode de précipitation. Les solides obtenus ont été soumis à une analyse thermogravimétrique couplée à l’analyse chromatographique des gaz émis. Les résultats montrent qu’au delà de la déshydratation, la décarbonatation se fait en deux étapes ; ce qui suggère la présence dans ces composés de carbonates ayant deux environnements différents. Une telle constatation a été déjà observée dans le cas de fluorapatites carbonatées exemptes d’ions sodium

Osteoinduction and antiosteoporotic performance of hybrid biomaterial chitosan-bioactive glass graft: effects on bone remodeling

International audienceOsteoinductive and antiosteroporotic phenomena could be created by using synthetic biomaterials for applications in bone surgery. In the present study, CH-based bioactive glass (BG-CH) with 17 wt% chitosan was elaborated by a freeze-drying process. BG-CH was implanted in the muscle and in the femoral condyles of ovariectomized rats. Grafted tissues were carefully removed for physico-chem. and histol. anal. Several physic-chem. techniques (XRD, FT-IR, MEB, ICP-OES and NMR) were employed to highlight the effects of chitosan on the glass matrix before and after implantation. The results of the study show that despite the non-addnl. osteogenic cells or agents, BG-CH is endowed with an osteoinductive property. After 8 wk, 13C NMR spectra showed the characteristic signals of γ-carbons of the hydroxyproline (71 ppm) abundant in collagen. γ-carboxyglutamate (55 ppm), which occurs in several other bone proteins like osteocalcin, indicating the BG-CH degrdn. and the dominance of the bone tissue formation. Moreover, this study showed a rise in Ca and P ion concns. in the implanted microenvironment, leading to the formation/deposition of Ca-P phases. Trace elements such as Zn and Fe were detected in the newly-formed bone and involved in the bone healing. The study highlights the suitability and the extensive applications of BG-CH composites and the clin. useful therapy in regenerative medicine