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Toxic Intermediates (toxic + intermediate)
Selected AbstractsChronic Ethanol Consumption Results in Atypical Liver Injury in Copper/Zinc Superoxide Dismutase Deficient MiceALCOHOLISM, Issue 2 2010Tiana V. Curry-McCoy Background:, Ethanol metabolism increases production of reactive oxygen species, including superoxide () in the liver, resulting in significant oxidative stress, which causes cellular damage. Superoxide dismutase (SOD) is an antioxidant enzyme that converts superoxide to less toxic intermediates, preventing accumulation. Because the absence of SOD would confer less resistance to oxidative stress, we determined whether damage to hepatic proteolytic systems was greater in SOD,/, than in SOD+/+ mice after chronic ethanol feeding. Methods:, Female wild-type (SOD+/+) and Cu/Zn-SOD knockout (SOD,/,) mice were pair-fed ethanol and control liquid diets for 24 days, after which liver injury was assessed. Results:, Ethanol-fed SOD,/, mice had 4-fold higher blood ethanol, 2.8-fold higher alanine aminotransferase levels, 20% higher liver weight, a 1.4-fold rise in hepatic protein levels, and 35 to 70% higher levels of lipid peroxides than corresponding wild-type mice. While wild-type mice exhibited fatty liver after ethanol administration, SOD,/, mice showed no evidence of ethanol-induced steatosis, although triglyceride levels were elevated in both groups of knockout mice. Ethanol administration caused no significant change in proteasome activity, but caused lysosomal leakage in livers of SOD,/, mice but not in wild-type mice. Alcohol dehydrogenase activity was reduced by 50 to 60% in ethanol-fed SOD,/, mice compared with all other groups. Additionally, while ethanol administration induced cytochrome P450 2E1 (CYP2E1) activity in wild-type mice, it caused no such induction in SOD,/, mice. Unexpectedly, ethanol feeding significantly elevated total and mitochondrial levels of glutathione in SOD knockout mice compared with wild-type mice. Conclusion:, Ethanol-fed SOD,/, mice exhibited lower alcohol dehydrogenase activity and lack of CYP2E1 inducibility, thereby causing decreased ethanol metabolism compared with wild-type mice. These and other atypical responses to ethanol, including the absence of ethanol-induced steatosis and enhanced glutathione levels, appear to be linked to enhanced oxidative stress due to lack of antioxidant enzyme capacity. [source] Treatment of an explosives plume in groundwater using an organic mulch biowallREMEDIATION, Issue 1 2009Farrukh Ahmad A field demonstration of a mulch permeable reactive barrier (PRB), or "biowall," as an in situ treatment technology for explosives in groundwater is summarized. Organic mulch consists of insoluble carbon biopolymers that are enzymatically hydrolyzed during decomposition to release aqueous total organic carbon (TOC). The released TOC is then available for microorganisms to use as an electron donor to transform electrophilic contaminants via reductive pathways. A 100-foot-long and 2-foot-thick mulch biowall was installed at the Pueblo Chemical Army Depot in Colorado to treat a shallow groundwater plume containing hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). To discourage groundwater flow bypassing around and under the biowall in this highly permeable formation, a hydraulic control was installed and the PRB was keyed into the bedrock. Technology performance was monitored using a monitoring well network to establish the development and extent of the downgradient treatment zone. Performance objectives of the field demonstration were: (1) greater than 90 percent removal of RDX across the PRB and the treatment zone; (2) an RDX concentration of less than 0.55 ,g/L in the treatment zone; and (3) cumulative toxic intermediate concentration (nitroso intermediates of RDX, MNX, DNX, and TNX) of less than 20 percent of the upgradient RDX concentration. All performance objectives were met within seven months after installation once the system reached a pseudo-steady state. By this point, a sustained reducing/treatment zone had been created downgradient of the mulch PRB that showed greater than 93 percent RDX removal, RDX concentrations less than 0.55 ,g/L, and no accumulation of toxic intermediates. The mulch biowall implemented during this demonstration was successful at meeting performance objectives while addressing the majority of potential concerns of the technology. © 2009 Wiley Periodicals, Inc. [source] Iron Absorption: Biochemical and Molecular Insights into the Importance of Iron Species for Intestinal UptakeBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2002Piero Cremonesi Redox chemistry of iron is particularly important in iron metabolism, both as a potential source of toxic intermediates and as an essential requirement for efficient iron transport. The initial step in iron absorption (uptake from lumen to mucosa) is particularly important and several pathways involving Fe(III) reduction or transport and Fe(II) transport have been identified. Novel genes associated with iron uptake include Dcytb, a putative iron-regulated reductase and DMT1, a Fe(II) carrier in the brush border membrane. Other mechanisms may also operate, however. We review the recent findings and apply this to understanding the absorption of Fe(III) pharmaceuticals. [source] Acute effect of antidiabetic 1,4-dihydropyridine compound cerebrocrast on cardiac function and glucose metabolism in the isolated, perfused normal rat heartCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2008Janina Briede Abstract Diabetes mellitus (DM) is an important cardiovascular risk factor and is associated with abnormalities in endothelial and vascular smooth muscle cell function, evoked by chronic hyperglycemia and hyperlipidemia. Chronic insulin deficiency or resistance is marked by decreases in the intensity of glucose transport, glucose phosphorylation, and glucose oxidation, plus decreases in ATP levels in cardiac myocytes. It is important to search for new agents that promote glucose consumption in the heart and partially inhibit extensive fatty acid beta-oxidation observed in diabetic, ischemia. When the oxygen supply for myocardium is decreased, the heart accumulates potentially toxic intermediates of fatty acid beta-oxidation, that is, long-chain acylcarnitine and long-chain acyl-CoA metabolites. Exogenous glucose and heart glycogen become an important compensatory source of energy. Therefore we studied the effect of the antidiabetic 1,4-dihydropyridine compound cerebrocrast at concentrations from 10,10,M to 10,7,M on isolated rat hearts using the method of Langendorff, on physiological parameters and energy metabolism. Cerebrocrast at concentrations from 10,10,M to 10,7,M has a negative inotropic effect on the rat heart. It inhibits L -type Ca2+channels thereby diminishing the cellular Ca2+ supply, reducing contractile activity, and oxygen consumption, that normally favors enhanced glucose uptake, metabolism, and production of high-energy phosphates (ATP content) in myocardium. Cerebrocrast decreases heart rate and left ventricular (LV) systolic pressure; at concentrations of 10,10,M and 10,9,M it evokes short-term vasodilatation of coronary arteries. Increase of ATP content in the myocytes induced by cerebrocrast has a ubiquitous role. It can preserve the integrity of the cell plasma membranes, maintain normal cellular function, and inhibit release of lactate dehydrogenase (LDH) from cells that is associated with diabetes and heart ischemia. Administration of cerebrocrast together with insulin shows that both compounds only slightly enhance glucose uptake in myocardium, but significantly normalize the rate of contraction and relaxation (,±,dp/dt). The effect of insulin on coronary flow is more pronounced by administration of insulin together with cerebrocrast at a concentration of 10,7,M. Cerebrocrast may promote a shift of glucose consumption from aerobic to anerobic conditions (through the negative inotropic properties), and may be very significant in prevention of cardiac ischemic episodes. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||