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Industrial and transport accidents, accidental releases during recreational swimming pool water treatment, household accidents due to mixing bleach with acidic cleaners, and, in recent years, usage of chlorine during war and in acts of terror, all contribute to the general and elevated state of alert with regard to chlorine gas. We here describe chemical and physical properties of [Cl.sub.2] that are relevant to its chemical reactivity with biological molecules, including water-soluble small-molecular-weight antioxidants, amino acid residues in proteins, and amino-phospholipids such as phosphatidylethanolamine and phosphatidylserine that are present in the lining fluid layers covering the airways and alveolar spaces. We further conduct a [Cl.sub.2] penetration analysis to assess how far [Cl.sub.2] can penetrate the surface of the lung before it reacts with water or biological substrate molecules. Our results strongly suggest that [Cl.sub.2] will predominantly react directly with biological molecules in the lung epithelial lining fluid, such as low-molecular-weight antioxidants, and that the hydrolysis of [Cl.sub.2] to HOCl (and HCl) can be important only when these biological molecules have been depleted by direct chemical reaction with [Cl.sub.2]. The results from this theoretical analysis are then used for the assessment of the potential benefits of adjuvant antioxidant therapy in the mitigation of lung injury due to inhalation of [Cl.sub.2] and are compared with recent experimental results. hypochlorite; lung epithelial lining fluid: antioxidants: exposure; therapy doi: 10.1152/ajplung.00077.2010.

S-adenosylmethionine (SAM) minimizes alcohol liepatotoxicity; however, the molecular mechanisms responsible for SAM hepatoprotection remain unknown. Herein, we use proteomics to determine whether the hepato-protective action of SAM against early-stage alcoholic liver disease is linked to alterations in the mitochondrial proteome. For this, male rats were fed control or ethanol-containing liquid diets [+ or -] SAM and liver mitochondria were prepared for proteomic analysis. Two-dimensional isoelectric focusing (2D IEF/SDS-PAGE) and blue native gel electrophoresis (BN-PAGE) were used to determine changes in matrix and oxidative phosphorylation (OxPhos) proteins, respectively. SAM co-administration minimized alcohol-dependent inflammation and preserved mitochondrial respiration. SAM supplementation preserved liver SAM levels in ethanol-fed rats; however, mitochondrial SAM levels were increased by ethanol and SAM treatments. With use of 2D IEF/SDS-PAGE, 30 proteins showed significant changes in abundance in response to ethanol, SAM, or both. Classes of proteins affected by ethanol and SAM treatments were chaperones, beta oxidation proteins, sulfur metabolism proteins, and dehydrogenase enzymes involved in methionine, glycine, and choline metabolism. BN-PAGE revealed novel changes in the levels of 19 OxPhos proteins in response to ethanol, SAM, or both. Ethanol- and SAM-dependent alterations in the proteome were not linked to corresponding changes in gene expression. In conclusion, ethanol and SAM treatment led to multiple changes in the liver mitochondrial proteome. The protective effects of SAM against alcohol toxicity are mediated, in part, through maintenance of proteins involved in key mitochondrial energy conserving and biosynthetic pathways. This study demonstrates that SAM may be a promising candidate for treatment of alcoholic liver disease. alcohol; liver steatosis; mitochondrial dysfunction; proteomics doi: 10.1152/ajpgi.00332.2009.

Chlorine ([Cl.sub.2]) is a highly reactive oxidant gas used extensively in a number of industrial processes. Exposure to high concentrations of C12 results in acute lung injury that may either resolve spontaneously or progress to acute respiratory failure. Presently, the pathophysiological sequelae associated with [Cl.sub.2]-induced acute lung injury in conscious animals, as well as the cellular and biochemical mechanisms involved, have not been elucidated. We exposed conscious Sprague-Dawley rats to [Cl.sub.2] gas (184 or 400 ppm) for 30 rain in environmental chambers and then returned them to room air. At 1 h after exposure, rats showed evidence of arterial hypoxemia, respiratory acidosis, increased levels of albumin, IgG, and IgM in bronchoalveolar lavage fluid (BALF), increased BALF surfactant surface tension, and significant histological injury to airway and alveolar epithelia. These changes were more pronounced in the 400-ppm-exposed rats. Concomitant decreases of ascorbate (AA) and reduced glutathione (GSH) were also detected in both BALF and lung tissues. In contrast, heart tissue AA and GSH content remained unchanged. These abnormalities persisted 24 h after exposure in rats exposed to 400 ppm C12. Rats injected systemically with a mixture of AA, deferoxamine, and N-acetyl-L-cysteine before exposure to 184 ppm [Cl.sub.2] had normal levels of AA, lower levels of BALF albumin and normal arterial P[o.sub.2] and Pc[o.sub.2] values. These findings suggest that [Cl.sub.2] inhalation damages both airway and alveolar epithelial tissues and that resulting effects were ameliorated by prophylactic administration of low-molecular-weight antioxidants. ascorbate; N-acetyl-L-cysteine; deferoxamine; arterial blood gases; alveolar permeability; minimum surface tension; airway epithelium; histology

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss [O.sub.2] toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen ([sup.3][O.sub.2]), and the more energetic, reactive singlet oxygen ([sup.1][O.sub.2]). Nitric oxide ([sup..]NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, [sup..]NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (C[O.sub.2]), and hydrogen sulfide ([H.sub.2]S). Like [sup..]NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (C[O.sub.3.sup..-]) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish 'cross talk' between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance. antioxidants; antioxidant defense and repair; nitric oxide; carbon dioxide; hydrogen sulfide; carbon monoxide; ozone; hydrogen peroxide; dissolved gases; oxidants doi:10.1152/ajpregu.00614.2005

The role of CO2 in the nitration and nitrosation by peroxyitrite is examined.

A viscosity test was carried out on peroxynitrite to determine the validity of the free radical theory that the rate of unimolecular decomposition is slower in high-viscosity solvents. The biological oxidant, which is a product of superoxide and nitric oxide, was not found to undergo single-bond homolysis to form free radical formation as the rate of rearrangements were not affected by changes in viscosity.