Alpha-Terpineol as Antitumor Candidate in Pre-Clinical Studies.

BACKGROUND: Alpha-terpineol is monoterpene alcohol with anti-tumor activity against different tumor cell lines (lung, breast, leukemias and colorectal) through blockage of NF-kB expression, which play an important role in tumor cells growth. OBJECTIVE: Evaluate the antitumor activity of alpha-terpineol in murine Sarcoma 180 cell line. METHODS: For the tests, different cytotoxic and genotoxic assays were used, including Trypan blue, cytokinesis- blocked micronucleus assay, comet assay, agarose gel DNA fragmentation, flow cytometry and cell viability using fluorescence. Ascitic fluid cells from sarcoma 180 were obtained from Mus musculus peritoneal cavity and Alpha-terpineol was tested at 100, 250 and 500 µg/mL. Doxorubicin and Cisplatin were used as positive controls. RESULTS: Cytotoxic effects of alpha-terpineol were found in all concentrations tested, reducing cell viability in 50.9; 38.53; 30.82% at 100, 250 and 500 µg/mL, respectively. Alpha-terpineol induced genotoxic effects due to DNA fragmentation (increased frequency and index of damage), and was clastogenic by increased micronuclei formation, nucleoplasmic bridges and nuclear buds. DNA fragmentation and increased cell death indicated that alpha-terpineol can cause early, late, and necrotic apoptosis. CONCLUSION: Our data indicate that alpha-terpineol has antitumor activity revealed by cytogenetic mechanisms and / or loss of cell membrane integrity.

Immobilization of papain enzyme on a hybrid support containing zinc oxide nanoparticles and chitosan for clinical applications.

A new hybrid bionanomaterial composed of zinc oxide nanoparticles (ZnO NPs) and chitosan was constructed after enzymatic immobilization of papain for biomedical applications. In this work, we report the preparation and characterization steps of this bionanomaterial and its biocompatibility in vitro. The properties of the immobilized papain system were investigated by transmission electron microscopy, zeta potential, DLS, UV-vis absorption spectroscopy, FTIR spectroscopy, and X-ray diffraction. The prepared bionanomaterial exhibited a nanotriangular structure with a size of 150 nm and maintained the proteolytic activity of papain. In vitro analyses demonstrated that the immobilized papain system decreased the activation of phagocytic cells but did not induce toxicity. Based on the results obtained, we suggest that the novel bionanomaterial has great potential in biomedical applications in diseases such as psoriasis and wounds.

Plant-Derived Butters as Lipid Nanocarriers: A Systematic and Prospective Review.

BACKGROUND: Pharmaceutical nanotechnology represents an efficient alternative for the delivery of pharmacologically active plant-derived compounds, considering their protective capacity, oral bioavailability and drug vectorization capacity. In this context, butters obtained from plant seeds have emerged as promising products for the development of pharmacologically active nanostructures. They possess a complex lipid composition, allowing the formation of different emulsion systems with solid cores, since this mixture of different triglycerides is solid at room temperature and body temperature. Therefore, the systematic mapping around the technological development of nanostructures produced from plant-derived butters is potentially valuable for researchers interested in novel alternative formulations for pharmacological therapy, with potential industrial, economic, health and societal impacts. METHODS: Systematic review was carried out by the search of scientific papers and patents deposited in official databases concerning the development of nanostructured pharmaceutical products using plantderived butters as starting material. The publications obtained were subjected to sorting and analysis by applying the following inclusion/exclusion criteria. RESULTS: The Solid Lipid Nanoparticle (SLN) was the type of nanostructure produced in all the analyzed scientific papers, due to the physicochemical characteristics of the lipid constituents of plantderived butters. In this sense, 54% of the articles have reported the use of Cocoa Butter for the production of nanostructures; 28% for Shea Butter; 6% for Cupuacu Butter, 6% for Murumuru Butter and 6% for Bacuri Butter. DISCUSSION: In the technological prospection, only two patents exhibited SLN as an invention based on cocoa butter and on shea butter, respectively. The production methods employed have included: phase inversion temperature, microemulsion, hot high pressure homogenization, high shear homogenization and ultrasonication. CONCLUSION: In light of this prospective review, the encouragement of novel studies in lipids-based nanotechnology is evident, considering the small number of findings so far, in order to stimulate new research involving plant-derived butters from easily cultivated fruits in tropical regions, then stimulating the pharmaceutical development of new therapeutic alternatives using biocompatible and sustainable raw materials.

Multiple P2X and P2Y receptor subtypes in mouse J774, spleen and peritoneal macrophages.

We investigated P2 receptor expression and function in macrophages from mouse, and in the J774 cell line, and revealed a larger spectrum of P2 receptor subtypes than previously recognised. The nucleotides adenosine triphosphate (ATP), adenosine diphosphate, uridine triphosphate and uridine diphosphate evoked an increase in intracellular calcium and the activation of a potassium current. The sensitivity of these responses to the antagonists suramin, PPADS, MRS 2179 and Cibacron blue suggest the presence of at least three functional P2Y receptor subtypes, most probably P2Y(2), P2Y(4) and P2Y(6). ATP also activated P2X receptors, giving rise to a rapidly activating cation conductance. This response was insensitive to the antagonists suramin and Cibacron blue, was potentiated by Zn(2+) and inhibited by acidification suggesting involvement of P2X(4) receptors. In low divalent cation solution, responses to ATP became larger, and dibenzoyl-ATP became more potent than ATP, indicating the presence of P2X(7) receptors. Immunofluorescence, flow cytometry, Western blots and RT-PCR show that P2X(4) and P2X(7) receptors are the most prominent in both macrophage types, while the expression of the other P2X subunits is variable and sometimes weak or undetectable. These techniques also demonstrated the presence of mRNA for P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptors along with protein expression for the three subtypes we investigated, namely, P2Y(1), P2Y(2) and P2Y(4).