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

Protective effect of umbelliferone on high-fructose diet-induced insulin resistance and oxidative stress in rats

Erythromycin estolate (EME), a potent macrolide antibiotic, generates free radicals, but their role in the development of liver toxicity is not yet well understood. The present study was carried out to investigate the effect of the antioxidant drug tetrahydrocurcumin (a metabolite of curcumin, the main component of turmeric) against EME-induced lipid peroxidation in rats. The oral administration of combined THC (80 mg/kg body weight) and EME (800 mg/kg body weight) for 15 days significantly decreased lipid peroxidation and enhanced cellular antioxidant defenses when compared with the group treated with EME alone. Supplemental histopathological examination of liver sections revealed that THC had a better antioxidant effect than Silymarin (200 mg/kg body weight), a reference drug. The results of this study indicate that THC affords significant protection against EME-induced lipid peroxidation.

Effect of tetrahydrocurcumin on erythromycin estolate-induced lipid peroxidation in rats.

We studied the effect of caffeic acid on alcohol-induced oxidative stress in alcohol-induced toxicity in rats. The elevation in the levels of lipid peroxidation in alcohol administration was accompanied by a significant decrease in the levels of vitamins C and E, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and glutathione S-transferase (GST) in the liver and kidney. Oral administration of caffeic acid at a dose of 12 mg/kg/body weight for 45 days significantly reduced the severe oxidative stress in alcohol toxicity as evidenced by the decrease in the levels of lipid peroxidation with a simultaneous increase in the level of enzymic and nonenzymic antioxidants in liver and kidney. Histological studies in the liver and kidney also showed that administration of caffeic acid to alcohol-treated rats resulted in a marked reduction in alcohol-induced pathological changes. These results suggest that administration of caffeic acid to alcohol-supplemen...

Beneficial effect of caffeic Acid on alcohol-induced alterations in lipid peroxidation and antioxidant defense in rats.

Cadmium (Cd) induces extensive membrane damage that contributes to the cytotoxic effect of Cd. We studied the effect of diallyl tetrasulfide (DTS) from garlic on Cd-induced changes in lipid peroxidation and membrane-bound enzymes in liver, kidney, and testis of rats. Cadmium exposure (3 mg/kg body weight, s.c) for 3 weeks induced a significant elevation in the levels of lipid peroxidation markers (thiobarbituric acid substances and lipid hydroperoxides) with a significant decrease in the activities of membrane bound ATPases (Na+/K+ ATPase, Ca2+ ATPase, Mg2+ ATPase), the indicators of membrane function in liver, kidney and testis. The oral administration of DTS (40 mg/kg body weight) along with Cd significantly decreased the level of lipid peroxidation and significantly restored the activities of membrane bound ATPases. The results of our study suggest that DTS attenuates lipid peroxidation in tissues and promotes the stability of the membrane by protecting it from Cd-induced alterations.

https://www.degruyter.com/view/j/jbcpp.2007.18.1/jbcpp.2007.18.1.37/jbcpp.2007.18.1.37.pdf

Diallyl tetrasulfide modulates the cadmium-induced impairment of membrane bound enzymes in rats.

1. The effects of Coccinia indica, an indigenous plant used in Ayurvedic medicine in India, on aortic collagen content and its characteristics were assessed in streptozotocin (STZ) diabetic rats. 2. Rats were made diabetic with a single intraperitoneal injection of STZ (45 mg/kg). Blood glucose, hydroxyproline, collagen, extent of glycation, collagen-linked fluorescence, soluble pattern of pepsin-soluble collagen, shrinkage temperature, alpha/beta ratio of type I collagen and type I/type III collagen ratio were determined in rats treated with C. indica leaf extract (CLEt; 200 mg/kg for 45 days using an oral intragastric tube). 3. In diabetic rats, the collagen content, as well as the degree of cross-linking, was increased, as evidenced by increased shrinkage temperature and decreased pepsin solubility. The alpha/beta ratio of type I collagen and the type I/type III collagen ratio of pepsin-soluble collagen were significantly decreased in STZ diabetic rats. 4. In conclusion, administration of CLEt for 45 days to STZ diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effects of C. indica (collagen content 23.87 +/- 1.52 mg/100 mg tissue (t value = 6.80), extent of cross-linking 0.893 +/- 0.072 mg hydroxyproline/100 mg tissue (t value = 9.0)) were comparable with those of glibenclamide (collagen content 26.18 +/- 1.65 mg/100 mg tissue (t value = 4.58), extent of cross-linking 0.787 +/- 0.057 mg hydroxyproline/100 mg tissue (t value = 7.1)), a reference drug.

Leelavinothan Pari

Papers

Protective effect of umbelliferone on high-fructose diet-induced insulin resistance and oxidative stress in rats

Effect of tetrahydrocurcumin on erythromycin estolate-induced lipid peroxidation in rats.

Beneficial effect of caffeic Acid on alcohol-induced alterations in lipid peroxidation and antioxidant defense in rats.

Diallyl tetrasulfide modulates the cadmium-induced impairment of membrane bound enzymes in rats.

Modulatory effect of Coccinia indica on aortic collagen in streptozotocin-induced diabetic rats.