Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

In this work we advance the hypothesis that omega-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes and attenuate effects of environmental exposures that activate molecules implicated in pathogenesis of vasoproliferative and neurodegenerative retinal diseases. These processes and exposures include ischemia, chronic light exposure, oxidative stress, inflammation, cellular signaling mechanisms, and aging. A number of bioactive molecules within the retina affect, and are effected by such conditions. These molecules operate within complex systems and include compounds classified as eicosanoids, angiogenic factors, matrix metalloproteinases, reactive oxygen species, cyclic nucleotides, neurotransmitters and neuromodulators, pro-inflammatory and immunoregulatory cytokines, and inflammatory phospholipids. We discuss the relationship of LCPUFAs with these bioactivators and bioactive compounds in the context of three blinding retinal diseases of public health significance that exhibit both vascular and neural pathology. How is omega-3 LCPUFA status related to retinal structure and function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a major structural lipid of retinal photoreceptor outer segment membranes. Biophysical and biochemical properties of DHA may affect photoreceptor membrane function by altering permeability, fluidity, thickness, and lipid phase properties. Tissue DHA status affects retinal cell signaling mechanisms involved in phototransduction. DHA may operate in signaling cascades to enhance activation of membrane-bound retinal proteins and may also be involved in rhodopsin regeneration. Tissue DHA insufficiency is associated with alterations in retinal function. Visual processing deficits have been ameliorated with DHA supplementation in some cases. What evidence exists to suggest that LCPUFAs modulate factors and processes implicated in diseases of the vascular and neural retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary intake. Certain LCPUFAs are selectively accreted and efficiently conserved within the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal cell gene expression, cellular differentiation, and cellular survival. DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production. Research on model systems demonstrates that omega-3 LCPUFAs also have the capacity to affect production and activation of angiogenic growth factors, arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs. Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression. VEGF plays an essential role in induction of: endothelial cell migration and proliferation, microvascular permeability, endothelial cell release of metalloproteinases and interstitial collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase. All four factors are associated with vascular instability. COX-2 drives conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our general conclusion is that there is consistent evidence to suggest that omega-3 LCPUFAs may act in a protective role against ischemia-, light-, oxygen-, inflammatory-, and age-associated pathology of the vascular and neural retina.

Integrated Systems Approach to Study the Role of Omega-3 Long-Chain Polyunsaturated Fatty Acids in Health and Disease of the Retina

municable disease control to the newer responsibilities of the hazards of ionizing radiation and medical defense against atomic attack. The individual topics are adequately developed with emphasis, in the majority, on brevity of presentation rather than complete and exhaustive detail. References are listed after each chapter for the reader desiring more definitive information. \"Epidemiologic Methods and Inferences\" by Dr. Dienfeld and \"Official and Voluntary Health Agencies\" by Dr. Hilleboe are two chapters which offer especially well-organized, succinct, and effective discussions of their respective subjects. The editors state in their preface that they are presenting \". . a new way to look at preventive medicine for the medical students, general practitioners, specialists, and professional workers in official and voluntary health agencies.\" In the opinion of the reviewer, the authors have achieved their purpose by editing a book which is more an introductory text than a reference tome.

Histochemistry, Theoretical and Applied.

Veterinary Clinical Pathology.

Textbook of biochemistry with clinical correlations , 4th edn TM Devlin, ed pp xvii + 1186, illustrated Wiley-Liss, New York, 1997 £2995, hardback

This beautifully illustrated and well-written book, with an impressive array of authors, is aimed at both undergraduate and postgraduate level As the editor states in the preface, it is not intended to be a compendium of biochemistry but rather emphasises the biochemistry of mammalian cells The first 22 chapters cover …

Textbook of biochemistry with clinical correlations

Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phyto-antioxidant, anti-inflammatory and anti-cancerous properties. The present study aimed to investigate the chemopreventive effect of SP against rat liver toxicity and carcinogenesis induced by dibutyl nitrosamine (DBN) precursors, and further characterized its underlying mechanisms of action in HepG2 cell line. Investigation by light and electron microscopy showed that DBN treatment induced severe liver injury and histopathological abnormalities, which were prevented by SP supplementation. The incidence of liver tumors was significantly reduced from 80 to 20% by SP. Immunohistochemical results indicated that both PCNA and p53 were highly expressed in the liver of DBN-treated rats, but were significantly reduced by SP supplementation. Molecular analysis indicated that SP treatment inhibited cell proliferation, which was accompanied by increased p21 and decreased Rb expression levels at 48hrs post-treatment. In addition, SP increased Bax and decreased Bcl-2 expression, indicating induction of apoptosis by 48hrs. This is the first report of the in vivo chemopreventive effect of SP against DBN-induced rat liver cytotoxicity and carcinogenesis, suggesting its potential use in chemoprevention of cancer.

/pdf/chemoprevention-of-rat-liver-toxicity-and-carcinogenesis-by-156m9ejt20.pdf

Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina.

Epidemiological reports have indicated a correlation between the increasing bisphenol A (BPA) levels in the environment and the incidence of male infertility. In this study, the protective effects of melatonin on BPA-induced oxidative stress and apoptosis were investigated in the rat testes and epididymal sperm. Melatonin (10 mg/kg body weight (bw)) was injected concurrently with BPA (50 mg/kg bw) for 3 and 6 weeks. The administration of BPA significantly increased oxidative stress in the testes and epididymal sperm. This was associated with a decrease in the serum testosterone level as well as sperm quality, chromatin condensation/de-condensation level, and the percentage of haploid germ cells in the semen. BPA administration caused a significant increase in apoptosis accompanied by a decrease in the expression of the antiapoptotic proteins Bcl-2 in the testes and epididymal sperm. The concurrent administration of melatonin decreased oxidative stress by modulating the levels of glutathione, superoxide di...

Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity.

Background: There is an increased interest in alternative treatments that reduce the toxicity of chemotherapy by lowering the drug concentration, whilst maintaining potency against cancer cells. Previous studies have demonstrated that arabinoxylan from rice bran, MGN- 3/Biobran, sensitizes human breast cancer cells (BCC) to daunorubicin (DNR). In the present study, we further evaluated the ability of MGN-3 to sensitize cells to another chemotherapy agent, paclitaxel. Materials and Methods: Non- metastatic MCF-7 (human BCC) and metastatic 4T1 (murine BCC) cells were cultured with different concentrations of paclitaxel in the presence or absence of MGN-3. Cell survival, DNA damage, and cell proliferation were examined. Results: MGN-3 increased the susceptibility of both types of cancer cells to paclitaxel by over 100-fold. Mechanistically, MGN-3 works synergistically with paclitaxel by causing DNA damage, enhancing apoptosis, and inhibiting cell proliferation in 4T1 cells. Conclusion: Our data demonstrate that MGN-3 is an effective chemosensitizer and may represent a novel adjuvant for the treatment of metastatic breast cancer. Cancer remains the largest cause of mortality in the world, claiming over six million lives each year. Chemotherapy is considered the cornerstone of treatment for many types of cancers. However, many chemotherapeutic agents exhibit dose-limiting toxicities (1-5). Therefore, there is increasing interest in identifying compounds that may increase the sensitivity of cancer cells to conventional chemotherapeutic agents, thus reducing chemotherapeutic-related toxicity (6-9). Early studies from our laboratory have shown that arabinoxylan rice bran, MGN-3/Biobran, sensitizes human leukemia HUT 78 cells to apoptosis induced by antibody to cluster of differentiation 95 (CD95) (10), and human breast cancer cells (BCCs) to daunorubicin in vitro (11). Further studies have revealed the synergistic effect of MGN-3 with transarterial oily chemoembolization in patients with hepatocellular carcinoma (12). In the present study, we thought it would be of particular interest to further investigate the chemosensitizing ability of MGN-3 towards another chemotherapeutic agent, paclitaxel, commonly known as taxol. Several rice bran products have been examined for their role as antitumor agents, including polysaccharide RBS (13), lipoprotein fraction (14), and agglutinin (RBA) (15). In addition, a recent study showed that rice (Oryza sativa L.) inhibits the growth of human leukemia U937 cells through activation of peripheral blood mononuclear cells (16). MGN- 3 is a natural product that is obtained by reacting rice bran hemicellulose with multiple carbohydrate-hydrolyzing enzymes from Shiitake mushrooms. The main chemical component of MGN-3 is arabinoxylan with a xylose in its main chain and an arabinose polymer in its side chain (17). We presented evidence elsewhere for the role of MGN-3 as a potent biological response modifier of human natural killer (NK) cells (18-20). It also activates human dendritic cells (21, 22), enhances the proliferation of T-cells and B-cells (17), and augments the phagocytic function of macrophages (23). In addition, further studies revealed that administration of MGN-3 to tumor-bearing mice resulted in significant reduction in tumor volume (24). Based on our earlier findings, we initiated this study to further investigate the chemosensitizing ability of MGN-3 towards another chemotherapeutic agent, paclitaxel, in metastatic breast cancer cells and to elucidate its mode of action.

Modified Arabinoxylan from Rice Bran, MGN-3/Biobran, Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

The current study was conducted to examine the antioxidant effect of grape seeds and skin (GSE and GSK) against Ehrlich solid tumor (EST)-induced oxidative stress, hepatic dysfunction and pathological changes in the liver of albino mice. GSE and GSK were mixed with the standard diet and given to mice 14 days before subcutaneous tumor cells inoculation and continued for 30 days. EST-bearing mice showed increase of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), elevation in lipid peroxidation (MDA) level accompanied by a decline in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels in blood and liver. Histopathologically and ultrastructurally, liver of EST bearing group showed hepatic degeneration with sinusoidal EST and lymphocytic infiltration, increase of collagen fibers, irregular nuclei, altered mitochondria and increase of secondary lysosomes. Histochemically, total protein and DNA contents were reduced in the liver of EST group. Conversely, GSE and GSK supplementation to EST bearing mice potentially recovered liver function enzymes, reduced MDA level, augmented antioxidant parameters, normalized liver protein and DNA contents and improved the pathologically examined hepatic lesions. In conclusion, GSE and GSK revealed potent antioxidant properties by augmenting the antioxidant defense system thereby protecting the liver against oxidative stress induced by Ehrlich solid carcinoma tumors.

https://cyberleninka.org/article/n/929099.pdf

Antioxidant and hepatoprotective activities of grape seeds and skin against Ehrlich solid tumor induced oxidative stress in mice

In this study, we examine the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the apoptotic effect of paclitaxel (Taxol) at low concentration [2 mg/kg body weight (BW)] in animals bearing Ehrlich ascites carcinoma (EAC) cells and elucidate its mechanisms of action. On Day 8 following tumor cells inoculation, mice bearing tumors were administered MGN-3 alone (40 mg/kg BW), paclitaxel alone, or MGN-3 plus paclitaxel. On Day 30 post-tumor inoculation, we observed significant suppression of tumor volume (TV) with paclitaxel alone (59%), MGN-3 alone (77%), and MGN-3 plus paclitaxel (88%). Inhibition of tumor growth post-treatment with both agents, as compared with either treatment alone, was associated with a decrease in cell proliferation, a marked increase in the sub-G0/G1 population, an increase in DNA damage and apoptosis of tumor cells, and a significant maximization of the apoptosis index (AI)/proliferation index (PrI) ratio. Histopathological and electron microscopy examination of the combined treatment group showed an increase in the degenerative regions of the solid tumor tissue and abundant apoptotic cells. These data suggest that MGN-3 supplementation enhances tumor cell demise in the presence of a low dose of chemotherapeutic agent via apoptotic mechanism.

Doaa A. Ali

Papers

Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina.

Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity.

Modified Arabinoxylan from Rice Bran, MGN-3/Biobran, Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

Antioxidant and hepatoprotective activities of grape seeds and skin against Ehrlich solid tumor induced oxidative stress in mice

Enhancing the Apoptotic Effect of a Low Dose of Paclitaxel on Tumor Cells in Mice by Arabinoxylan Rice Bran (MGN-3/Biobran).