https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.

Therapeutic potential of resveratrol: the in vivo evidence.

Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.

Mitochondrial Membrane Permeabilization in Cell Death

Recent studies demonstrated accumulation of arachidonic acid secondary to the loss of membrane phospholipids in an ischemic myocardium.' Since the bulk of the arachidonate in mammalian heart is esterified in the fatty acyl chains of glycerophospholipids' and the free arachidonic acid level in heart should represent a balance between the liberation of the acid by hydrolysis and its re-esterification into complex lipids by acyltransferases,' we undertook a study to examine the fate of free arachidonic acid in the ischemic heart.

Metabolism and Turnover of Arachidonic Acid in Ischemic Myocardium

Publisher Summary This chapter focuses on the pharmacological effects of the adenosine triphosphate (ATP)-sensitive class of potassium channel blockers and openers on the function of the ischemic-reperfused myocardium. The importance of ATP-sensitive potassium channel (K+ATP) blockers and openers is recognized in the regulation of stress-induced, functional changes in the myocardium (example, by ischemia, reperfusion, and preconditioning) and this recognition is having a major impact on the regulation of cardiac function in ischemic-reperfused hearts. The use of (K+ATP) blockers or openers is not always beneficial and may have some detrimental effects, especially in the ischemic-reperfused myocardium. The chapter also discusses (K+ATP) channel openers. The properties of KATPchannels vary according to the type of tissue, and at least three major classes are currently recognized: (1) the type I channels, blocked by micromolar concentrations of intracellular ATP, are present in cardiac, skeletal, smooth muscle, and pancreatic β cells. The pancreatic β cell is the more sensitive to ATP, and these cells are sensitive to voltage and calcium ions. (2) The type II channel, originally described in neurons is inhibited by millimolar concentrations of ATP. (3) The type III channel, found in tracheal smooth muscle and some epithelial cells, is similar to the type II in its sensitivity to ATP, but differs in being activated by micromolar concentrations of calcium.

The Role of ATP-Sensitive Potassium Channels in Myocardial Ischemic Stress

Role of Coenzyme Q10 in Myocardial Tolerance to Ischemia and Reperfusion

Pulmonary oxygen toxicity, a progressive process that destroys cells in the lung, has been attributed to the generation of oxygen-derived free radicals within the pulmonary circulation.' Polyunsaturated lipids and phospholipids are particularly susceptible to free-radical reactions. and injury to these molecules may account for the observed free-radical pathology? In this study free radicals were generated within the pulmonary circulation, and lung phospholipid contents were estimated in order to further clarify the pathophysiology of pulmonary toxicity.

Phospholipase Inhibition Protects the Lung from Free-Radical Injury

The unique properties of embryonic stem (ES) cells to self-renew indefinitely or to differentiate to any cell type (pluripotency) warrants their clinical application in regenerative medicine. MicroRNAs are crucial for post-transcriptional gene regulation and, thus, remain an essential element of the regulation of ES cells. The present review discusses the essential elements of microRNAs that regulate the life and death of ES cells.

Dipak K. Das

Papers

Metabolism and Turnover of Arachidonic Acid in Ischemic Myocardium

The Role of ATP-Sensitive Potassium Channels in Myocardial Ischemic Stress

Role of Coenzyme Q10 in Myocardial Tolerance to Ischemia and Reperfusion

Phospholipase Inhibition Protects the Lung from Free-Radical Injury

MicroRNA signatures of stem cells