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This MiniReview describes the essential biochemical and molecular aspects of matrix metalloproteinases (MMPs) and briefly discusses how they engage in different diseases, with particular emphasis on cardiovascular diseases. There is compelling scientific evidence that many MMPs, especially MMP-2, play important roles in the development of cardiovascular diseases; inhibition of these enzymes is beneficial to many cardiovascular conditions, sometimes precluding or postponing end-organ damage and fatal outcomes. Conducting comprehensive discussions and further studies on how MMPs participate in cardiovascular diseases is important, because inhibition of these enzymes may be an alternative or an adjuvant for current cardiovascular disease therapy.

Leishmaniasis is caused by species of the protozoan parasite Leishmania. It is the third most important vector-borne disease and is widely distributed throughout the world. The World Health Organization recommends pentavalent antimonials as drugs of first choice in its treatment. Although Glucantime has traditionally been used to treat leishmaniasis, there are still many questions about its structure, mechanisms of action and ability to induce damage in DNA. In this study, the genotoxic activity of this drug was evaluated in vitro using human lymphocytes treated for 3 and 24 h (comet assay) and 48 h (apoptosis assay) with 3.25, 7.5 and 15 mg/ml of Glucantime, respectively, corresponding to 1.06, 2.12 and 4.25 mg/ml of pentavalent antimony. In the in vivo tests, Swiss mice received acute treatment with three doses (212.5, 425 and 850 mg/kg) of pentavalent antimony. All the treatments were administered intraperitoneally in the volumes of 0.1 ml/10 g of body weight, adapting human exposure to murine conditions. The animals were treated for 3 h in the comet assay using resident peritoneal exudate macrophages, for 24 h in the comet assay using peripheral blood leukocytes and for 24 h in the bone marrow erythrocyte micronucleus test. While no genotoxic effect was observed in the in vitro tests, the in vivo tests showed that Glucantime induces DNA damage. These findings indicate that Glucantime is a promutagenic compound that causes damage to DNA after reduction of pentavalent antimony (SbV) into the more toxic trivalent antimony (SbIII) in the antimonial drug meglumine antimoniate.

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The findings of this study showed that the ethanol concentrations of tested drinks affect the physical properties of the investigated acrylic resin. An obvious plasticizing effect was found, which could lead to a lower in vivo durability associated with alcohol consumption.

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Increased reactive oxygen species (ROS) formation may enhance matrix metalloproteinase (MMP)-2 activity and promote cardiovascular dysfunction. We show for the first time that MMP-2 is upstream of increased ROS formation and activates signaling mechanisms impairing redox balance. Incubation of vascular smooth muscle cells (VSMC) with recombinant MMP-2 increased ROS formation assessed with dihydroethidium (DHE) by flow cytometry. This effect was blocked by the antioxidant apocynin or by polyethylene glycol-catalase (PEG-catalase), and by MMP inhibitors (doxycycline or GM6001). Next, we showed in HEK293 cells that MMP-2 transactivates heparin-binding epidermal growth factor (HB-EGF) leading to EGF receptor (EGFR) activation and increased ROS concentrations. This effect was prevented by the EGFR kinase inhibitor Ag1478, and by phospholipase C (PLC) or protein kinase C (PKC) inhibitors (A778 or chelerythrine, respectively), confirming the involvement of EGFR pathway in MMP-2-induce responses. Next, we showed that intraluminal exposure of aortas to MMP-2 increased vascular MMP-2 levels detected by immunofluorescence and gelatinolytic activity (by in situ zimography) in association with increased ROS formation. This effect was inhibited by MMP inhibitors (phenanthroline or doxycycline) and by apocynin or PEG-catalase. MMP-2 also increased aortic contractility to phenylephrine and this effect was prevented by MMP inhibitor GM6001 and by apocynin or PEG-catalase, showing again that increased ROS formation mediates functional effects of MMP-2. These results show that MMP-2 activates the EGFR and triggers downstream signaling pathways increasing ROS formation and promoting vasoconstriction. These findings may have various implications for cardiovascular diseases.

BackgroundThe babassu palm tree is native to Brazil and is most densely distributed in the Cocais region of the state of Maranhão, in northeastern Brazil. In addition to the industrial use of refined babassu oil, the milk, the unrefined oil and the nuts in natura are used by families from several communities of African descendants as one of the principal sources of food energy. The objective of this study was to evaluate the effects of babassu oil on microvascular permeability and leukocyte-endothelial interactions induced by ischemia/reperfusion using the hamster cheek pouch microcirculation as experimental model.MethodsTwice a day for 14 days, male hamsters received unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18 ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations were made in the cheek pouch and macromolecular permeability increase induced by ischemia/reperfusion (I/R) or topical application of histamine, as well as leukocyte-endothelial interaction after I/R were evaluated.ResultsThe mean value of I/R-induced microvascular leakage, determined during reperfusion, was significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001). In addition, histamine-induced increase of microvascular permeability was significantly less pronounced in BO groups compared to MO one. No significant differences among groups in terms of leukocyte adhesion, concentrations of tumor necrosis factor alpha, interleukin 1, and interleukin 6 were found.ConclusionsOur findings suggest that unrefined babassu oil reduced microvascular leakage and protected against histamine-induced effects in postcapillary venules and highlights that these almost unexploited nut and its oil might be secure sources of food energy.