Production of Cell Damage

Acute pancreatitis has been induced in dogs by retrograde intraductal injections of 5% hydrogen peroxide solution and sunflower oil (Keleman and Torok, 1990) and in rats by continuous infusion of xanthine/XO or hydrogen peroxide into the coeliac artery (Tamura et al., 1991a). Xanthine/XO has also been shown to be toxic, as measured by release of LDH, to in vitro rat pancreatic acini (Tamura et al., 1991b). 

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Production of Mucosal Damage 2.3.1.2.1 Cell culture Stimulated neutrophils are known to be cytotoxic to cells in vitro (Dull et al., 1987 Dallegri et al., 1990 Grisham et al., 1990b). Several in vitro systems have been used to demonstrate oxidative damage to intestinal cells. Xanthine/XO increased Cr release and decreased [ H]thymidine uptake by IEC-18 small intestinal epithelial cell monolayers in a dose-dependent manner (Ma et al., 1991). Rat enterocytes show decreased trypan blue exclusion and increased protein release when incubated with neutrophils stimulated... 

Phenolic oxidation by PPO and POD in B-deficient leaves leads to the production of quinones. These compounds are known for their high toxicity, and for being responsible for the production of oxygenated radicals such as H2O2 and O2. The accumulation of quinones in plants that act as indicators of the deficiency has been considered as the prime cause of cell damage and of growth reduction [127]. 

Answer Defects in Complex II result in increased production of ROS, damage to DNA, and mutations that lead to unregulated cell division (cancer). It is not clear why the cancer tends to occur in the midgut. 

Cells contain about 70% water, and the radiation is largely absorbed by interaction with the water molecules and formation of ions, free radicals and excited molecules. The ions may react at ionizable positions of the DNA (e.g. phosphate groups). Radicals, such as OH and H, and oxidizing products, such as H2O2, may be added at unsaturated bonds or they may break the bonds between two helices. Excited molecules may transfer the excitation energy to the DNA and also cause breaks. A great number of different products of DNA damage have been identified. 

Fig.25.8). The Kupffer cells are probably activated by a product of the damaged hepatocytes, such as necrotic debris, iron, ROS, acetaldehyde, or aldehyde products of lipid peroxidation. Kupffer cells also may produce acetaldehyde from ethanol internally through their own MEOS pathway. 

Protection by 3-aminobenzamide is not mediated by an inhibition of ADP-ribosylation. At high concentrations (20 mM), benzamide and analogs inhibited 0 production from TPA-stimulated granulocytes, whUe die corresponding acids did not (Table 1). However, when analyzed in the cytotoxicity test, it was foimd that benzamide and nicotinamide at 2.5 mM concentrations did not prevent but enhanced cytotoxicity. This pointed to a special scavenger function of ABA in the prevention of cell damage as induced by reactive oxygen species. Protection by ABA was also observed... 

Based on this pathway of cell death, it appears likely that agents which can alter NAD or ATP metabolism should be useful in sensitizing cells to the cytotoxic effects of some chemotherapeutic agents whose mechanism of action involves the production of DNA damage. Both 6-aminonicotinamide (6-AN) and Tiazofurin (Taz) have already been shown to interfere at multiple steps of pyridine nucleotide metabolism. Taz has been shown to produce the Taz analog of NAD (8, 9), to interfere with NAD synthesis and... 

Figure 1 Flavonoids and their in vivo metabolite forms may act by direct reaction with oxidizing species in the body, thereby reducing the accumulation of end products of oxidative damage in the cell, or by modulation of intracellular signaling events.

An expandable anode involves compression of the anode stmcture using cHps during cell assembly so as not to damage the diaphragm already deposited on the cathode (Eig. 3a). When the cathode is in position on the anode base, 3-mm diameter spacers are placed over the cathode and the cHps removed from the anode. The spring-actuated anode surfaces then move outward to bear on the spacers, creating a controlled 3-mm gap between anode and cathode (Eig. 3b). This design has also been appHed to cells for the production of sodium chlorate (22). 

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