Oxidative stress plays a major role in the pathogenesis of various diseases including neurodegenerative diseases, myocardial ischemia-reperfusion injury and cancer. Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5,-dione], the principal yellow pigment isolated from turmeric (Curcuma longa Linn), is known as a potent antioxidant comparable to a-tocopherol. Its antioxidant activities have been studied in several in vitro models. 1) Despite its poor bioavailability, 2-4) the therapeutic benefits of curcumin in animals have been demonstrated in several oxidative stress models such as Alzheimer's disease, 5) ethanol induced oxidative injury in brain, liver, heart and kidney, 6,7) and myocardial ischemic damage.8) It is possible that the metabolites of curcumin could mediate major antioxidant activities in vivo.In mouse, curcumin is first biotransformed to dihydrocurcumin (DHC) and tetrahydrocurcumin (THC) and these compounds are subsequently converted to monoglucuronide conjugates including curcumin-glucuronide, dihydrocurcuminglucuronide and tetrahydrocurcumin-glucuronide. 9) In human and rat hepatocytes, curcumin is metabolized into curcumin glucuronide, curcumin sulfate, THC, hexahydrocurcumin (HHC) and octahydrocurcumin (OHC). 10,11) Antioxidant activities of THC have already been studied both in vitro and in vivo. Venkatesan et al. 12) reported that THC had higher activity than curcumin in protecting the nitrite induced oxidation of haemoglobin and lysis of erythrocytes. THC has also been demonstrated to be more potent than curcumin in protection against ferric nitrilotriacetate (Fe-NTA) induced oxidative renal damage in mice. 13) THC produces this protective effect to cells against oxidative stress by scavenging of free radicals, 14) inhibition of lipid peroxidation and formation of hydroperoxides. 15) To the best of our knowledge, the antioxidant activities of HHC and OHC have not been reported.We are also interested in the antioxidant activities of natural demethoxyl derivatives of curcumin, demethoxycurcumin (Dmc) and bisdemethoxycurcumin (Bdmc), which are always found together with curcumin in tumeric extracts and in commercial preparation of curcumin. Antioxidant activities of Dmc and Bdmc have been reported in the model systems of hydroxyl radical induced DNA damage, 16) DPPH radical scavenging activity 17) and recently in lipid peroxidation. 18)However, to date, there has been no comparative study on the antioxidant activities of curcumin with its natural demethoxy derivatives and metabolite hydrogenated derivatives. In particular, the ability to provide protection against lipid and cell membrane damage of all of those derivatives has not yet been reported. The aim of this study is to compare the antioxidant activities of curcumin, its demethoxy derivatives (Dmc and Bdmc), and hydrogenated derivatives (THC, HHC and OHC) using three in vitro models: radical scavenging activity by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, AAPH [2,2Ј-azobis(2-amidinopropane)dihydrochloride] induced linole...
Gastrointestinal (GI) leakage is believed to exacerbate sepsis and new, validated markers of GI barrier performance might benefit clinical decision-making. Serum (1→3)-β-D-glucan (BG) was evaluated as a potential GI leakage marker. Serum BG was tested in several mouse models of GI leakage, including dextran sulfate solution (DSS) administration, endotoxin (LPS) injection, and cecal ligation and puncture sepsis (CLP). Serum BG titer was also evaluated in patients with sepsis and septic shock, for comparison.With 0.75% DSS administration, BG increased only after oral administration of heat-killed C. albicans, but increased spontaneously with 1.5% DSS. In the LPS and CLP models, BG increased as early as 1 h and at 12 h after LPS administration and surgery, respectively. GI leakage was confirmed by orthogonal validation methods including FITC-dextran oral administration in the DSS, LPS, and CLP models and, in the DSS model, with urine sucralose after oral administration and serum endotoxemia. IL-6 increased in parallel with serum BG. Serum BG or IL-6, at 18 h, anticipated sepsis mortality in the CLP model.Analysis of serum BG from patients with febrile neutropenic sepsis (N = 49) and febrile non-neutropenic sepsis (N = 39) demonstrated BG elevation. Patients with bacterial septic shock had serum BG titers similar to levels observed in invasive fungal disease, regardless of febrile neutropenia. Serum BG was lower in less severe cases of bacterial sepsis. Elevated serum IL-6 was associated with GI leakage and elevated serum BG.Serum BG may have potential as a sepsis/septic shock biomarker and further study in this context is warranted.
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