Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

http://demystifyingmedicine.od.nih.gov/DM15/m3d17/reading01.pdf

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

Article de synthese sur le metabolisme de la methionine, acide amine essentiel, chez les mammiferes. Etude du schema metabolique, de la regulation du metabolisme (mise en evidence et importance relative de chaque facteur). Etude de la transamination de la methionine, du role de la S-adenosyl-methionine, de l'oxydation de l'homocysteine et de la cystathionine. Etude du disfonctionnement du metabolisme et des consequences chez les hommes

Methionine metabolism in mammals.

The present invention provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Retinoic acids and derivatives thereof, and paclitaxel. Also provided are methods for embolizing blood vessels, and eliminating biliary, urethral, esophageal, and tracheal/bronchial obstructions.

Anti-angiogenic compositions and methods of use

Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration

Acetaldehyde adducts with proteins: binding of [14C]acetaldehyde to serum albumin.

https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1081&context=veterans

Role of malondialdehyde-acetaldehyde adducts in liver injury.

Previous studies have shown that ethanol feeding to rats alters methionine metabolism by decreasing the activity of methionine synthetase. This is the enzyme that converts homocysteine in the presence of vitamin B12 and N5-methyltetrahydrofolate to methionine. The action of the ethanol results in an increase in the hepatic level of the substrate N5-methyltetrahydrofolate but as an adaptive mechanism, betaine homocysteine methyltransferase, is induced in order to maintain hepatic S-adenosylmethionine at normal levels. Continued ethanol feeding, beyond 2 months, however, produces depressed levels of hepatic S-adenosylmethionine. Because betaine homocysteine methyltransferase is induced in the livers of ethanol-fed rats, this study was conducted to determine what effect the feeding of betaine, a substrate of betaine homocysteine methyltransferase, has on methionine metabolism in control and ethanol-fed animals. Control and ethanol-fed rats were given both betaine-lacking and betaine-containing liquid diets for 4 weeks, and parameters of methionine metabolism were measured. These measurements demonstrated that betaine administration doubled the hepatic levels of S-adenosylmethionine in control animals and increased by 4-fold the levels of hepatic S-adenosylmethionine in the ethanol-fed rats. The ethanol-induced infiltration of triglycerides in the liver was also reduced by the feeding of betaine to the ethanol-fed animals. These results indicate that betaine administration has the capacity to elevate hepatic S-adenosylmethionine and to prevent the ethanol-induced fatty liver.

Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration.

Alcohol breakdown in the liver results in the generation of the reactive molecule acetaldehyde and, as a byproduct, highly reactive oxygen-containing molecules known as oxygen radicals. Both acetaldehyde and oxygen radicals can interact with proteins and other complex molecules in the cell, forming hybrid compounds called adducts. Other adducts are formed with aldehyde molecules, which are produced through the interaction of oxygen radicals with lipids in the cells. Adduct formation impedes the function of the original proteins participating in the reaction. Moreover, the adducts may induce harmful immune responses. Both of these effects may account for some of the damage observed in alcoholic liver disease. Adduct formation has been shown to occur in the livers of humans and animals consuming alcohol and to start and predominate in those liver regions that show the first signs of liver damage.

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Dean J. Tuma

Papers

Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration

Acetaldehyde adducts with proteins: binding of [14C]acetaldehyde to serum albumin.

Role of malondialdehyde-acetaldehyde adducts in liver injury.

Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration.

Dangerous byproducts of alcohol breakdown--focus on adducts