4-hydroxy-2-nonenal and dityrosine

Chronic ethanol intoxication induces oxidative stress participating in the development of many diseases. Nutrition and the interaction of food nutrients with ethanol metabolism may modulate alcohol toxicity. One such compound is l-carnitine (l-3-hydroxy-4-N,N,N-trimethylaminobutyrate), which also reveals antioxidant abilities. The present study has been designed to investigate the effect of l-carnitine as an antioxidant on the serum and liver of rats chronically intoxicated with ethanol. Rats received l-carnitine solution (1.5g/1L) for 5 weeks and/or were treated intragastrically with ethanol for 4 weeks. In the serum and liver, the level of nonenzymatic antioxidants and lipid and protein oxidation markers were determined. It was shown that alcohol caused the increase in the level of lipid peroxidation products-conjugated dienes (by about 70% and 60% in the liver and blood serum, respectively), malondialdehyde (MDA) (by about 60% and 30% in the liver and blood serum, respectively), 4-hydroxynonenal (4-HNE) (by about 35% and 25% in the liver and blood serum, respectively), and changes in the level of protein oxidative markers-increase in dityrosine and decrease in tryptophan (by about 40%) in the serum and liver of rats. Moreover, the decrease in vitamin E level (by about 30%) and the level of glutathione (GSH) (by about 20% in the liver and blood serum) was also observed. Administration of l-carnitine to rats intoxicated with ethanol significantly protects lipids and proteins against oxidative modifications in the serum and liver. The level of conjugated dienes, MDA, and 4-HNE was decreased by about 30%, 30%, and 20% in the liver, respectively, and by about 20%, 10%, and 10% in the blood serum in comparison to the ethanol group. Moreover, the level of tryptophan was increased and dityrosine decreased by about 10% and 20% in the liver, respectively, and by about 30% and 10% in the blood serum in comparison to the ethanol group. l-carnitine partially protects nonenzymatic antioxidants against oxidative stress. The level of vitamin E was increased by about 20% and the level of GSH was increased by about 25% in the liver and blood serum in comparison to the ethanol group. It is possible that beneficial effect of l-carnitine is connected with its abilities to scavenge free radicals and to chelate metal ions.

Topics: Aldehydes; Animals; Antioxidants; Carnitine; Ethanol; Glutathione; Lipid Metabolism; Lipid Peroxidation; Liver; Male; Malondialdehyde; Oxidative Stress; Proteins; Rats; Rats, Wistar; Tryptophan; Tyrosine; Vitamin E

Cooking-oil-fumes containing toxic components may induce reactive oxygen species (ROS) to oxidize macromolecules and lead to acute lung injury. Our previous study showed that a decaffineated green tea extract containing (+)-catechin, (-)-epicatechin, (+)-gallocatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate can inhibit oxidation, inflammation, and apoptosis. We determined whether the catechins supplement may reduce cooking-oil-fumes-induced acute lung injury in rat. In the urethane-anesthetized Wistar rat subjected to 30-120 min of cooking-oil-fumes exposure, blood ROS significantly increased in the recovery stage. After 30-min cooking-oil-fumes exposure, the enhanced blood ROS level further increased in a time-dependent manner during the recovery stage (321 +/- 69 counts/10 s after 1 h, 540 +/- 89 counts/10 s after 2 h, and 873 +/- 112 counts/10 s after 4 h). Four hours after 30-min cooking-oil-fumes exposure, lung lavage neutrophils and ROS as well as lung tissue dityrosine and 4-hydroxy-2-nonenal increased significantly. Two weeks of catechins supplememnt significantly reduced the enhanced lavage ROS, lung dityrosine and 4-hydroxy-2-nonenal level. Cooking-oil-fumes-induced oxidative stress decreased lung Bcl-2/Bax ratio and HSP70 expression, but catechins treatment preserved the downregulation of Bcl-2/Bax ratio and HSP70 expression. We conclude that catechins supplement attenuates cooking-oil-fumes-induced acute lung injury via the preservation of oil-smoke induced downregulation of antioxidant, antiapoptosis, and chaperone protein expression.

Topics: Acute Lung Injury; Aldehydes; Animals; Apoptosis; bcl-2-Associated X Protein; Catechin; Cooking; Dietary Supplements; Disease Models, Animal; Female; HSP70 Heat-Shock Proteins; Oils; Oxidative Stress; Pneumonia; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Reactive Oxygen Species; Time Factors; Tyrosine

4-hydroxynonenal (HNE) is a highly toxic product of lipid peroxidation (LPO). Its role in the inhibition of cytochrome c oxidase activity and oxidative modifications of mitochondrial lipids and proteins were investigated. The exposure of mitochondria isolated from rat heart to HNE resulted in a time- and concentration-dependent inhibition of cytochrome c oxidase activity with an IC50 value of 8.3 +/- 1.0 microM. Immunoprecipitation-Western blot analysis showed the formation of HNE adducts with cytochrome c oxidase subunit I. The loss of cytochrome c oxidase activity was also accompanied by reduced thiol group content and increased HNE-lysine fluorescence. Furthermore, there was a marked increase in conjugated diene formation indicating LPO induction by HNE. Fluorescence measurements revealed the formation of bityrosines and increased surface hydrophobicity of HNE-treated mitochondrial membranes. Superoxide dismutase + catalase and the HO* radical scavenger mannitol partially prevented inhibition of cytochrome c oxidase activity and formation of bityrosines. These findings suggest that HNE induces formation of reactive oxygen species and its damaging effect on mitochondria involves both formation of HNE-protein adducts and oxidation of membrane lipids and proteins by free radicals.

Topics: Aldehydes; Animals; Dose-Response Relationship, Drug; Electron Transport Complex IV; Lipid Peroxidation; Male; Membrane Lipids; Mitochondria, Heart; Oxidation-Reduction; Rats; Rats, Wistar; Reactive Oxygen Species; Tyrosine