Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of...

Bioavailability of curcumin: problems and promises.

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.

Silver nanoparticles (Ag-np) are being used increasingly in wound dressings, catheters, and various household products due to their antimicrobial activity. The toxicity of starch-coated silver nanoparticles was studied using normal human lung fibroblast cells (IMR-90) and human glioblastoma cells (U251). The toxicity was evaluated using changes in cell morphology, cell viability, metabolic activity, and oxidative stress. Ag-np reduced ATP content of the cell caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. DNA damage, as measured by single cell gel electrophoresis (SCGE) and cytokinesis blocked micronucleus assay (CBMN), was also dose-dependent and more prominent in the cancer cells. The nanoparticle treatment caused cell cycle arrest in G2/M phase possibly due to repair of damaged DNA. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. The transmission electron microscopic (TEM) analysis indicated the presen...

Cytotoxicity and Genotoxicity of Silver Nanoparticles in Human Cells

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

The present investigation was carried out to evaluate the effect of N-benzoyl-D-phenylalanine (NBDP) and metformin on blood glucose, plasma insulin, and on the fatty acid composition of total lipids in the livers and kidneys of control and experimental diabetic rats. When compared with nondiabetic control rats, neonatal streptozotocin (nSTZ) diabetic rats showed a significant increase in blood glucose and decreased plasma insulin. Analysis of fatty acids revealed a significant increase in the concentration of palmitic, stearic, and oleic acids in liver and kidney, whereas linolenic and arachidonic acids were significantly decreased. In diabetic rats, the oral administration of combined NBDP/metformin for 6 wk decreased the high concentrations of palmitic, stearic, and oleic acids and elevated the low levels of linolenic and arachidonic acids. The results suggest that the NBDP/metformin combination exhibits both antidiabetic and antihyperlipidemic effects in nSTZ diabetic rats and prevents the fatty acid changes produced during diabetes.

Combined n-benzoyl-d-phenylalanine and metformin treatment reverses changes in the fatty acid composition of streptozotocin diabetic rats.

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of type 2 diabetes. The aim of the study was to investigate the effect of EMS and metformin administration on tail collagen content and its characteristics in streptozotocin-nicotinamide-induced type 2 diabetic rats. EMS was administered intraperitoneally for 30 days to normal and diabetic rats. In the diabetic rats, a significant increase in the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content was absorbed with a significant decrease in the level of insulin, hemoglobin in streptozotocin-nicotinamide diabetic rats. Moreover, a daily administration of nonglucidic nutrient EMS and metformin significantly decreased the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content, whereas it increased insulin, hemoglobin levels in diabetic rats. The positive influence of nonglucidic nutrient on both collagen content and its properties suggests a potential mechanism for the ability of EMS to delay diabetic complications.

Effect of succinic acid monoethyl ester on hemoglobin glycation and tail tendon collagen properties in type 2 diabetic rats.

The aim of the study was to investigate the protective effect of N-benzoyl-D-phenylalanine (NBDP), an antidiabetic compound, on the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in normal and streptozotocin-induced diabetic cataract in wistar rats. Cholinesterases activities were significantly decreased with significant increase in lipid peroxidation as reflected by Thiobarbituric Acids Reactive Substances (TBARS) in the diabetic rats. This, in turn, could lead to alterations associated with diabetes complications. Treatment with NBDP appears to have reversed this effect. The decreased activity of cholinesterases observed in diabetes may be due to lack of insulin, which causes specific alterations in neurotransmitter, thus causing retinal dysfunction. NBDP could protect against direct action of lipid peroxidation on retina AChE and BChE and in this way it might be useful in the prevention of cholinergic retinal dysfunction in diabetes.

Modulatory Effect of N-Benzoyl-D-Phenylalanine on Cholinesterases in Rat Retinas of Neonatal Streptozotocin Diabetic Rats

Objective: The aim of the current study is to evaluate the effect of pterostilbene (PTS), on deranged plasma and tissue glycoprotein components in high-fat-diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. \nMethods: The experimental duration was 16 weeks. The C57BL6/J mice were fed a normal diet, normal diet with PTS, HFD, and STZ injection (10th week only), and diabetic mice with PTS for the past 6 weeks. \nResults: A significant increase in glycoprotein components such as hexose, hexosamine, fucose, and sialic acid (SA) in plasma was observed in diabetic mice. In hepatic and renal tissues, a significant decrease in SA with an increase in other glycoprotein components was detected in diabetic mice when compared with control mice. Oral administration of PTS significantly improved the glycoprotein levels in plasma and tissues of diabetic mice to near normal level. \nConclusion: In this study, we resolved that PTS improves disturbed glycoprotein metabolism in HFD and STZ-induced type 2 diabetic mice.

Protective role of pterostilbene on plasma and tissue glycoprotein components in high-fat diet-fed and streptozotocin-induced type 2 diabetic mice

Diabetes is a common disease in the whole world, which has an increasing prevalence (Mousavi et al., 2012). Type 2 diabetes mellitus is a metabolic disorder that reduces the body's ability to glucose uptake. Factors causing diabetes are still unknown, although genetic factors, obesity and the absence of physical activity have an important role in diabetes (Beckert et al., 2006). Diabetes mellitus leads to hyperglycemia, blood lipid disorders, including hypertriglyceridemia and low HDL-cholesterol and increased oxidative stress (Murarka and Movahed, 2010). Uncontrolled diabetes can cause diabetic complications, which increase medical costs and decrease quality of life (Goldberg, 2003).

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Leelavinothan Pari

Papers

Combined n-benzoyl-d-phenylalanine and metformin treatment reverses changes in the fatty acid composition of streptozotocin diabetic rats.

Effect of succinic acid monoethyl ester on hemoglobin glycation and tail tendon collagen properties in type 2 diabetic rats.

Modulatory Effect of N-Benzoyl-D-Phenylalanine on Cholinesterases in Rat Retinas of Neonatal Streptozotocin Diabetic Rats

Protective role of pterostilbene on plasma and tissue glycoprotein components in high-fat diet-fed and streptozotocin-induced type 2 diabetic mice

Effect of Pterostilbene on cardiac oxidative stress on high-fat diet-fed and Streptozotocin-induced type 2 diabetic mice