Reactive oxygen species alcohol

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Aminolevulinic acid (ALA HCl, Levulan Kerastick) is indicated for the treatment of nonhyperkeratotic actinic keratosis of the face and scalp. It has two components, an alcohol solution vehicle and ALA HCl as a dry solid. The two are mixed prior to application to the skin. When applied to human skin, ALA is metabolized to protoporphyrin, which accumulates and on exposure to visible light produces a photodynamic reaction that generates reactive oxygen species (ROS).The ROS produce cytotoxic effects that may explain therapeutic efficacy. Local burning and stinging of treated areas of skin due to photosensitization can occur. 

Alcohol-related liver diseases are complex, and ethanol has been shown to interact with a large number of molecular targets. Ethanol can interfere with hepatic lipid metabolism in a number of ways and is known to induce both inflammation and necrosis in the liver. Ethanol increases the formation of superoxide by Kupffer cells thus implicating oxidative stress in ethanol-induced liver disease. Similarly prooxidants (reactive oxygen species) are produced in the hepatocytes by partial reactions in the action of CYP2E1, an ethanol-induced CYP isoform. The formation of protein adducts in the microtubules by acetaldehyde, the metabolic product formed from ethanol by alcohol dehydrogenase, plays a role in the impairment of VLDL secretion associated with ethanol. 

Figure 8.8 The catalytic cycle of the CYP enzymes. The substrate binds to a hydro-phobic site of the enzyme (I —> II). This leads to a shift in the valence electrons of iron, from low-spin to high-spin status, and an uptake of an electron from cytochrome P450 reductase (II —> III). Oxygen is then added (III —> IV) to the iron and another electron is added (IV V). Some of the intermediates may lose reactive oxygen species (IV —> II), which has harmful consequences for the cell. There are some electronic rearrangements (V —> VI —> VII). The product (RO) leaves the enzyme and its ground state is restored (VII —> I). RO is often more toxic than the substrate (R) and may be an alcohol, a phenol, or an epoxide that can be rendered harmless by other enzymes and made ready for excretion.

JNK-1 and c-fos proteins were significantly induced in the ischaemic/reperfused Langendorff rat heart, which was inhibited by a proanthocyanidin extract (Sato et al. 2001). In concert, red grape seed proanthocyanidin water-alcohol extract significantly reduced the appearance of reactive oxygen species and apoptotic cardiomyocytes in the is-chaemic/reperfused hearts. 

Ros. Reactive oxygen species RESINS. Natural products that either occur naturally as plant exudates or are prepared by alcohol extraction of botanicals that contain resinous principles. Naturally occurring resins... 

The increased activity of P450 enzymes also leads to an enhanced production of free radicals. Ethanol can scavenge hydroxyl radicals (OH°) to form hydroxyethyl free radicals during MEOS activity but other free radicals such as 02° are also produced. These reactive oxygen species will bind to DNA, RNA and proteins, thus compromising DNA and protein function and potentially stimulating production of autoantibodies which are found in higher levels in alcoholics. 

Figure 29.2 Illustration of the neutralising role of glutathione (GSH) on reactive oxygen species such as hydrogen peroxide, and its regeneration by the consumption of NADPH. NADPH is consumed by MEOS during alcohol metabolism, thus increasing...

Figure 29.6 Possible routes of ethanol to cancer. This schematic diagram shows some of the ways in which it is suspected that ethanol may promote carcinogenesis. Although not carcinogenic itself, ethanol can solubilise organic carcinogens that can intercalate between the bases of DNA and cause it to be misread. The metabolism of alcohol generates large amounts of free radicals and reactive oxygen species. These cause peroxidation of lipids and the products of lipid peroxidation can form adducts with DNA and its repair enzymes. The acetaldehyde produced by alcohol oxidation can also do this, but can also induce cell proliferation in some tissues as well as altering the levels of steroid hormones upon which some tumours depend.

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