We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in myocardial phosholipid degradation and cellular injury during reperfusion of ischemic myocardium. For this purpose, isolated rat hearts were perfused with isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty acids (P less than 0.05) after 30 min of reperfusion following 30 min of normothermic global ischemia compared with hearts preperfused with nonimmune immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated hearts were associated with significantly (P less than 0.05) higher radiolabel in all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune immunoglobulin G-treated hearts. Measurement of phospholipase activity in subcellular organelles of these hearts showed decreased PLA2 activity in cytosol, mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC activity of microsomes in anti-PLC-treated hearts. Furthermore, both the antiphospholipases attenuated the release of creatine kinase and lactate dehydrogenase into perfusate and increased contractility as well as coronary flow in the reperfused hearts. Results of this study suggest that both PLA2 and PLC are involved in the degradation of phospholipids and cellular injury that occur during reperfusion of ischemic myocardium.
Inflammatory bowel disease (IBD) is associated with activation of nuclear factor kappa B (NF-kappaB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin-3,3'-digallate (TFDG), the most potent anti-oxidant polyphenol of black tea, down-regulates NF-kappaB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines.The in vivo efficacy of TFDG was assessed in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Both mRNA and protein levels of proinflammatory cytokines and iNOS were analyzed in colon tissue treated with or without TFDG. NF-kappaB activation was determined by electrophoretic mobility shift assay and levels of NF-kappaB inhibitory protein (IkappaBalpha) were analyzed by Western blotting.Oral administration of TFDG (5 mg kg(-1) daily i.g.) significantly improved TNBS-induced colitis associated with decreased mRNA and protein levels of TNF-alpha, IL-12, IFN-gamma and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-kappaB activation and IkappaBalpha depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IkappaBalpha and higher activity of IkappaB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-kappaB, cytosolic IKK activity and preserved IkappaBalpha in colon tissue.TFDG exerts protective effects in experimental colitis and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-kappaB activation.
The present study was conducted to investigate the absorption, distribution and pharmacokinetics of TFDG in mice for which it was labeled with 125I. For comparison, the radiolabeled polyphenol was given either along with Black Tea Extract (BTE) or as pure TFDG. Following intravenous (5 mg kg-1) or intragastric (500 mg kg-1) administration, plasma and tissue levels were quantified by radioactive counting and the results were analysed by the SPSS program. Although lower than intravenous dosing, maximum plasma concentration (Cmax) for TFDG was achieved at 6 h post-oral dosing with an AUC0-α of 504.92 g min L-1, which was 20 fold higher than that for i.v. dosing. Maximum radioactivity (42%) was recovered in kidney following i.v., administration, whereas for oral administration maximum radioactivity (0.07%) was recovered in liver as revealed by tissue distribution studies. Uptake of TFDG was > 4-fold more efficient in hepatocytes than in non parenchymal cells. However, TFDG showed better absorption by various organs as well as by liver cells when given along with BTE. Moreover, a second equal administration of TFDG after 6 h interval enhanced tissue levels of radioactivity above those after a single administration. These results point towards a wide distribution of 125I-TFDG in mouse organs and suggest that frequent consumption of black tea may be better for increased systemic availability of polyphenols.
1 Inflammmatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of proinflammatory cytokines. In this study, we have investigated the protective effects of curcumin, an anti-inflammatory and antioxidant food derivative, on 2,4,6- trinitrobenzene sulphonic acid-induced colitis in mice, a model for IBD. 2 Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa), increased serine protease activity (may be involved in the degradation of colonic tissue) and high levels of malondialdehyde (an indicator of lipid peroxidation). 3 Dose-response studies revealed that pretreatment of mice with curcumin (50 mg kg(-1) daily i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. Higher doses (100 and 300 mg kg(-1)) had comparable effects. 4 In curcumin-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon as well as decreased serine protease activity. 5 Curcumin also reduced the levels of nitric oxide (NO) and O(2)(-) associated with the favourable expression of Th1 and Th2 cytokines and inducible NO synthase. Consistent with these observations, nuclear factor-kappaB activation in colonic mucosa was suppressed in the curcumin-treated mice. 6 These findings suggest that curcumin or diferuloylmethane, a major component of the food flavour turmeric, exerts beneficial effects in experimental colitis and may, therefore, be useful in the treatment of IBD.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
