Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats.

The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4mg/kg bw/day), ChlA (5mg/kg bw/day) or the combination OTA (0.4mg/kg bw/day)+ChlA (5mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA+ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism.

Modulation of in vitro murine B-lymphocyte response by curcumin.

Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (tumeric). It was previously described that curcumin had a potent anti-inflammatory effect and inhibited the proliferation of a variety of tumor cells. In the present study, we investigated the inhibitory effects of curcumin on the response of normal murine splenic B cells. Curcumin inhibited the proliferative response of purified splenic B cells from BALB/c mice stimulated with the Toll-like receptor ligands LPS and CpG oligodeoxynucleotides. LPS-induced IgM secretion was also inhibited by curcumin. The proliferative response induced by either the T-independent type 2 stimuli anti-delta-dextran or anti-IgM antibodies was relatively resistant to the effect of curcumin. We investigated the intracellular signaling events involved in the inhibitory effects of curcumin on murine B cells. Curcumin did not inhibit the increase in calcium levels induced by anti-IgM antibody. Western blotting analysis showed that curcumin inhibited TLR ligands and anti-IgM-induced phosphorylation of ERK, IkappaB and p38. Curcumin also decreased the nuclear levels of NFkappaB. Our results suggested that curcumin is an important inhibitor of signaling pathways activated upon B cell stimulation by TLR ligands. These data indicate that curcumin could be a potent pharmacological inhibitor of B cell activation.

Increased immunoglobulin secretion by B lymphocytes from Trypanosoma cruzi infected mice after B lymphocytes-natural killer cell interaction.

In the present study, we investigated whether natural killer (NK) cells modulate immunoglobulin (Ig) secretion by B cells from Trypanosoma cruzi-infected mice. B cells from infected mice increased IgM and IgG2a secretion in the presence of a NK cell line, and this response was cell contact-dependent. Stimulation of splenic B cells with polyinosinic-polycytidylic acid, a NK cell activator, also increased Ig secretion by B cells from infected mice. B cells from infected mice expressed higher levels of the B7.2 molecule. Our results suggest that NK cells may be involved in the control of the abnormal B cell activation observed during T. cruzi infection.

Ligation of CD4 concomitant to activation induces primary CD4+ T-cell adhesion and pseudopodia formation in vitro.

A regulatory function for CD4 molecules in lymphocyte adhesion and motility was investigated. Murine splenic CD4+ T cells, activated in the presence of phorbol ester and immobilized anti-CD4 mAb, adhered to the plastic surface and formed extended cytoplasmic projections (pseudopodia). Pseudopod formation was cell-density-dependent, peaked at Day 3, and disappeared by Day 5 in culture. This response could be inhibited by soluble anti-CD4 and by RGD-containing peptide. Ligation of CD4 was required at a late stage in cell activation, and stimulated cell motility in vitro. Addition of IL-4, but not IL-2, upregulated pseudopod formation induced by suboptimal stimuli. Anti-IL-4 mAb blocked pseudopod formation, and exogenous IL-4 restored the response. A combination of IL-4 plus phorbol ester, but not IL-2 plus phorbol ester, induced pseudopod formation in concert with CD4 ligation. Exogenous IL-2, on the other hand, blocked pseudopod formation. CD45RBlow CD4+ T cells were much more efficient than CD45RBhigh CD4+ T cells for pseudopod formation. These results indicate that CD4 ligation induces CD4+ T-cell adhesion and motility, mainly in the memory/activated subset, which might be relevant for immune responses in vivo.

2-5A synthetase expression in mice infected with Trypanosoma cruzi.

This study describes the production and action of interferon in mice infected with Colombian and Y strain T. cruzi. The production of interferon was monitored by an in vitro assay of plasma and extract of spleen, lung and heart for interferon activity. The action of interferon in mice was assessed by measuring an interferon-mediated enzyme activity, 2-5A synthetase. Infected mice (strain Balb/c) were sacrificed at different time intervals, and the level of this enzyme was measured in extracts of spleen, lung and heart. Colombian strain infection induced higher levels of interferon than Y strain under the same conditions; consequently, a greater increase in 2-5A synthetase induction was observed in the former of the two strains. These results suggest that interferon produced by T. cruzi infected mice is active, since a variety of organs respond to its presence by producing elevated levels of 2-5A synthetase.