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We recently showed that mammary cytosolic xanthineoxidoreductase had the ability to bioactivate ethanol (EtOH) to acetaldehyde (AC) and free radicals. In the present study, we report that the microsomal fraction also biotransforms EtOH to AC. One pathway requires NADPH and the others do not. Both need oxygen. The NADPH-dependent pathway is not inhibited by CO:O(2) (80:20) or SKF 525A and that excludes the participation of cytochrome P450. It is inhibited by diethyldithiocarbamate (DDTC), sodium azide, and diphenyleneiodonium (DPI) but not by desferrioxamine, which suggests a possible role of a non-iron copper-requiring flavoenzyme. The process was partially inhibited by thiobenzamide (TBA), methylmercaptoimidazole (MMI), and nordihydroguaiaretic acid (NDG) but not by dapsone, aminotriazole, or indomethacin. These results suggest the potential participation of flavine monooxygenase and of lipooxygenase or of peroxidases/oxidases having similar characteristics but not of lactoperoxidase or cyclooxygenase. The pathway not requiring NADPH could also be partially inhibited by DDTC, NDG, azide, DPI, and TBA or MMI but not by the other chemicals. Little activity proceeds under nitrogen. Oxidases or peroxidases might be involved. No formation of 1-hydroxyethyl radicals was detected either in the presence or absence of NADPH. The nature of the EtOH bioactivating enzymes involved remains to be established. However, the fact remains that an activation of EtOH to AC was found in mammary tissue and could have a significant effect in some stages of the process of breast tumor promotion by EtOH.

Nifurtimox (Nfx) and Benznidazole (Bz) are being used for the treatment of the acute phase of Chagas' disease. Recently, they were also considered for use in the indeterminate phase. Both the nitroheterocyclic drugs have serious toxic side effects. The mechanism of Nfx toxicity is associated with the formation of reactive oxygen species (ROS) generated during nitroreduction. Potential effects on cardiac function have not been established yet, despite the well-known cardiopathy often produced by the disease itself. We describe experiments testing some acute effects of Nfx on the male Sprague Dawley rat heart. Nifurtimox was present in the heart at 1, 3 and 6 h after intragastric (i.g) treatment. In vitro studies on Nfx microsomal and cytosolic nitroreductase activities showed that only the microsomal fraction had the ability to nitroreduce it. Cytochrome P450 and cytochrome P450 reductase would be involved in the process as suggested by their response to specific inhibitors. Nifurtimox increased the cardiac protein carbonyl content at 1 and 3 h and decreased the protein sulfhydryl content at 3 h. In addition, 24 h after treatment ultrastructural alterations such as marked cytoplasmic vacuolization, separation and loss of myofibrils and mitochondrial swelling were observed. Results suggest that Nfx administration might aggravate pre-existing adverse cardiac conditions. Human & Experimental Toxicology (2007) 26, 781 — 788

CCM fortified versions of orange and apple juice have high Ca absorbability and are potentially important vehicles for increasing dietary Ca intake. The greater Ca absorption from CCM-AJ compared with CCM-OJ is accounted for by differences in the carbohydrate and organic acid content of the juices. These data suggest that by modifying common beverage ingredients, products with even greater Ca absorbability could be formulated.

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