RESUMO
BACKGROUND: Myeloperoxidase (MPO), in the presence of hydrogen peroxide and a halide represent an efficient microbicidal mechanism of phagocytic cells. MPO is abundant in neutrophils which also respond to infection by producing large amounts of reactive oxygen species (ROS). MPO, ROS and halide constitute a very toxic antimicrobial system (called the Klebanoff system or KS). Resting mature macrophages do not contain granular MPO and thus are unable to kill pathogenic mycobacteria and some other microorganisms by this system. EXPERIMENTAL: Under the hypothesis that transforming macrophages into peroxidase-positive (PO(+)) cells, these cells would be able to kill Mycobacterium tuberculosis, in this study, mature macrophages were loaded with exogenous peroxidase and were tested for their capacity to kill the Mycobacterium in the presence or in the absence of hydrogen peroxide. RESULTS: It was found that PO-loaded macrophages eagerly ingest M. tuberculosis, but do not show a significant mycobactericidal activity on this microorganism despite that it is highly susceptible to the Klebanoff system in vitro. Failure of PO-loaded macrophages to kill M. tuberculosis may obey either to an inappropriate location of the exogenous PO in these cells or more likely, to the presence of efficient detoxifying mechanisms in the bacteria. On the contrary, MPO-loaded or unloaded macrophages efficiently killed Listeria monocytogenes. CONCLUSION: The lack of granular MPO in mature macrophages, and the predilection of mycobacteria to infect these cells are two situations that favor the development of tuberculosis and related diseases, such as leprosy and Buruli ulcer.
RESUMO
2,4,5-trimethoxycinnamic acid (TMC), the major and non toxic metabolite of alpha-asarone (2,4,5-trimethoxy-1-propenyl benzene), retains most of the pharmacological properties of alpha-asarone, since both substances, administered to hypercholesterolemic rats at 80 mg/kg body wt, decreased total serum cholesterol, lowered LDL-cholesterol levels and kept unaffected HDL-cholesterol levels. In addition, both substances increased bile flow, especially in hypercholesterolemic rats, by rising the secretion of bile salts, phospholipids and bile cholesterol. These drugs also reduced cholesterol levels of gallbladder bile, whereas phospholipids and bile salts concentrations were increased, decreasing the cholesterol saturation index (CSI). We also found that alpha-asarone was 20 times better inhibitor of HMG-CoA reductase than TMC. This effect on HMG-CoA reductase was the only property highly reduced in TMC in comparison with alpha-asarone, while the other pharmacological properties of alpha-asarone were retained by TMC. These experiments strongly suggest that TMC can be further studied as a possible hypocholesterolemic and cholelitholytic agent.