Antiproliferative activity of extracts of Euphorbia tirucalli L (Euphorbiaceae) from three regions of Brazil

Purpose: To investigate Euphorbia tirucalli extract for probable geographic variations in its antiproliferative activity.Methods: The aerial parts of E. tirucalli were collected in the Brazilian states of Mato Grosso, Rio de Janeiro, Pará, Minas Gerais and Santa Catarina. The 70 % ethanol extract was obtained according to the procedure described in Brazilian Homeopathic Pharmacopeia. The antiproliferative activity of extracts, in concentrations of 62, 125, 250, and 500 μg mL-1, was tested against leukemia (HL-60), lymphoma (Daudi) and melanoma (B16F10) cell lines using methyl thiazol tetrazolium assay (MTT). Phytochemical analysis were carried out using High-performance liquid chromatography-diode array (HPLC-UV-DAD) and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(-) FT-ICR MS) assays.Results: There was significant regional variability in the cytotoxicity of E. tirucalli extracts in a dosedependent manner. The extracts had similar activity towards leukemia cell line HL-60, decreasing cell viability to about 60 – 70 %. The extract showed the presence of ellagitannins, flavonoids, veracylglucan, and acid triterpenes as the major compounds.Conclusion: While the results support the ethnopharmacological use of E. tirucalli throughout Brazil, regional quantitative differences found in some classes of secondary metabolites may explain the variations observed in antitumor activity.Keywords: Aveloz, Cancer, Cytotoxicity, Antiproliferative, Ethnopharmacological, Traditional medicin

In Vitro Activities of Iboga Alkaloid Congeners Coronaridine and 18-Methoxycoronaridine against Leishmania amazonensis

In previous studies, we demonstrated the leishmanicide effect of coronaridine, a natural indole alkaloid isolated from stem bark of Peschiera australis (Delorenzi et al., Antimicrob. Agents Chemother. 45:1349-1354, 2001). In this study we show the leishmanicidal effect of the synthetic coronaridine and its racemic 18-methoxylated analog, 18-methoxycoronaridine. Both alkaloids revealed a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their potent leishmanicide effect, both alkaloids were neither toxic to murine macrophages nor did they modulate their oxidative or cytokine production responses

The contralateral kidney presents with impaired mitochondrial functions and disrupted redox homeostasis after 14 days of unilateral ureteral obstruction in mice.

In unilateral ureteral obstruction (UUO), both oxidative stress and mitochondrial dysfunction are related to cell death. The aim of this study has been to characterize profiles of enzyme antioxidant activities and mitochondrial functioning of the contralateral (CL) compared to UUO and Sham (false-operated) kidneys of Balb/c mice. Kidneys were resected 14 days after obstruction for immunohistochemical and cortical mitochondrial functioning assays. Antioxidant enzymes activities were investigated in mitochondria and cytosol. Oxygen consumption (QO2) and formation of O2 reactive species (ROS) were assessed with pyruvate plus malate or succinate as the respiratory substrates. QO2 decreased in CL and UUO in all states using substrates for complex II, whereas it was affected only in UUO when substrates for complex I were used. Progressive decrease in mitochondrial ROS formation-in the forward and reverse pathway at complex I-correlates well with the inhibition of QO2 and, therefore, with decreased electron transfer at the level of complexes upstream of cytochrome c oxidase. CL and UUO transmembrane potential responses to ADP were impaired with succinate. Intense Ca2+-induced swelling was elicited in CL and UUO mitochondria. Important and selective differences exist in CL antioxidant enzymes with respect to either Sham or UUO kidneys: CL kidneys had increased mitochondrial glutathione peroxidase and cytosolic catalase activities, indicative of compensatory responses in the face of an early altered ROS homeostasis (as detected by 4-hydroxynonenal), and of a significant tendency to apoptosis. In CL and UUO, upregulation of nuclear (erythroid-derived 2)-like 2 transcription factor (Nrf2), as well as of cytoplasmic and nuclear Kelch-like ECH-associated protein 1 (Keap1) in opposition to decreased heme oxygenase-1 (HO-1), suggest impairment of the Nrf2/Keap1/HO-1 system. It is concluded that chronic obstruction impairs mitochondrial function in CL and UUO, preferentially affecting complex II

The Cutaneous Infiltrates of Leprosy — Cellular Characteristics and the Predominant T-Cell Phenotypes

We report on the characteristics of cells in the cutaneous lesions and blood of 21 patients with lepromatous, tuberculoid, and intermediate forms of leprosy. A large proportion of the infiltrates in lepromatous lesions consist of macrophages heavily parasitized with Mycobacterium leprae. The T cells in the lesions are devoid of OKT4/Leu 3a-positive ("helper") cells and consist almost exclusively of OKT8/Leu 2a-positive ("suppressor") populations. In contrast, the tuberculoid infiltrates contain well-organized epithelioid and giant-cell granulomas and only remnants of bacilli, and the predominant T cell is from the OKT4/Leu 3a-positive subset. In both tuberculoid and lepromatous infiltrates, T cells and macrophages expressed HLA-DR antigen. No marked alteration in the distribution of blood T-cell phenotypes was noted. We conclude that there is a marked difference between T-cell subsets in lepromatous and tuberculoid infiltrates, which may influence the microbicidal activity of macrophages in the lesions