thiourea and indole-3-carbinol

Cruciferous vegetables contain glucobrassicin which, during metabolism, yields indole-3-carbinol (I3C). The aim of this study was to find whether indole-3-carbinol caused apoptosis and its mechanism in Candida albicans. We found that treatment of Candida albicans with indole-3-carbinol significantly increased the reactive oxygen species and hydroxyl radical accumulation. The hydroxyl radical is one of the most active components of oxygen, and it is the end product of an oxidative damage cellular death pathway. We investigated the general phenotypes of apoptosis and then investigated whether there were other distinct markers of apoptosis. Furthermore, the effects of thiourea as a hydroxyl radical scavenger and protective effect of trehalose, which is the result of the fungal immune system, was also assured. This study indicates that indole-3-carbinol has apoptosis effects, including a production of hydroxyl radicals, cytochrome c release and activation of metacaspase. Both hydroxyl radicals and metacaspases triggered apoptosis in Candida albicans.

Topics: Annexin A5; Antifungal Agents; Apoptosis; Biomarkers; Candida albicans; Cytochromes c; Drug Evaluation, Preclinical; Free Radicals; Glucosinolates; In Situ Nick-End Labeling; Indoles; Membrane Potential, Mitochondrial; Microbial Sensitivity Tests; Molecular Targeted Therapy; Reactive Oxygen Species; Thiourea

The present study was performed to determine the effects of neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible ANG II-dependent malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats (n = 7) were fed a normal diet containing indole-3-carbinol (I3C; 0.3%) for 6-9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were assessed in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC; 1 mg/h). In hypertensive Cyp1a1-Ren2 rats, l-SMTC increased MAP from 169 +/- 3 to 188 +/- 4 mmHg (P < 0.01), which was a smaller increase than in noninduced rats (124 +/- 9 to 149 +/- 9 mmHg, P < 0.01, n = 5). Additionally, l-SMTC decreased renal plasma flow (RPF) to a similar extent (-34 +/- 13 vs. -35 +/- 12%) in the hypertensive and normotensive rats (4.1 +/- 0.2 to 2.7 +/- 0.5 and 3.1 +/- 0.3 to 2.0 +/- 0.3 ml x min(-1) x g(-1), respectively, P < 0.01) but did not alter glomerular filtration rate (GFR) in either group. In additional experiments, administration of the COX-2 inhibitor, nimesulide (3 mg/kg i.v.), during simultaneous infusion of l-SMTC decreased MAP in both hypertensive and noninduced rats (182 +/- 2 to 170 +/- 3 mmHg and 153 +/- 3 to 140 +/- 3 mmHg, respectively, P < 0.01). Nimesulide also decreased RPF (1.9 +/- 0.2 to 0.8 +/- 0.1 ml x min(-1) x g(-1), P < 0.01) and GFR (0.9 +/- 0.1 to 0.4 +/- 0.1 ml x min(-1) x g(-1), P < 0.01) in hypertensive rats but did not alter RPF or GFR in noninduced rats. The present findings demonstrate that both nNOS-derived NO and COX-2 metabolites exert pronounced renal vasodilator influences in hypertensive Cyp1a1-Ren2 rats. The data also indicate that the renal vasodilator effects of COX-2-derived prostanoids in hypertensive Cyp1a1-Ren2 rats are not dependent on nNOS activity.

Topics: Angiotensin II; Animals; Animals, Genetically Modified; Blood Pressure; Citrulline; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Cytochrome P-450 CYP1A1; Enzyme Inhibitors; Hypertension, Malignant; Indoles; Kidney; Male; Nitric Oxide Synthase Type I; Rats; Regional Blood Flow; Renin; Sulfonamides; Thiourea; Vasoconstriction