Phosphorylated abacavir analogue (ABC-1) has ameliorative action against Newcastle disease virus induced pathogenesis in chicken.

Newcastle disease virus (NDV) causes huge economic loss to the poultry industry due to high mortality and morbidity. The present study aimed to assess the protective role of novel phosphorylated analogue ABC-1 in vivo in NDV-infected chickens through the inhibition of fusion protein. Both NDV-induced oxidative damage and protective role of novel phosphorylated ABC-1 were evaluated in vital organs such as the liver and lung of chickens. Enzyme linked immunosorbent assay (ELISA) results showed that protein oxidation and nitration levels were significantly raised in NDV-infected tissues compared to healthy controls, whereas these levels were reduced significantly (P < 0.05) in birds treated with phosphorylated compounds compared to the NDV-infected group alone. Additional investigation with double immunofluorescence showed that the large amount of immuno colocalization and Western blot analysis also confirmed this observation through its band pattern in NDV-infected birds compared to healthy birds, whereas these alterations were reduced in treatment with novel phosphorylated ABC-1. The expression of fusion glycoprotein was studied by immuno colocalization, PCR, and flow cytometry, and results demonstrated that the novel phosphorylated analogues reduced the expression of fusion glycoprotein. These results put forth that novel phosphorylated ABC-1 protects chickens from NDV-induced pathogenesis, protein oxidation/nitration, and exerts potent antiviral activity.

Size Dependent Uptake and Hemolytic Effect of Zinc Oxide Nanoparticles on Erythrocytes and Biomedical Potential of ZnO-Ferulic acid Conjugates.

Despite zinc oxide nanoparticles (ZnONPs) being increasingly used as carriers in biomedical fields due to their multifaceted properties and therapeutic importance, better understanding of the mechanisms and cellular consequences resulting from their interaction with cells and cellular components has been warranted. In the present study, we investigate the size-dependent interaction of ZnONPs on RBCs, and its impact on cell viability, DNA damage, ROS generation and morphological changes, employing cellular and analytical methods. Size, charge, stability and solubility were confirmed by DLS, zeta potential, ICP-AES and TEM analysis. Further ICP-AES, TEM, spectroscopic observations and cell based assays showed that ZnONPs exhibited a size dependent impact on RBCs and haemoglobin (Hb), particularly size <50 nm. Conversely, ferulic acid (FA) conjugates and serum albumin significantly reduced the adverse effects exhibited by ZnONPs. The extent of DNA damage and ROS generation is comparatively low in ZnONPs-FA than in ZnONPs alone treated cells. Thus our study documents a novel conceptualization delineating the influence of size on the material properties and therapeutic potential of nanoparticle.

Effect of troxerutin on 2-aminoanthracene and DNA interaction and its anti-mutagenic property.

One of the pivotal mechanisms projected for bioflavonoids in cancer chemoprevention is through their intervention against mutagen-DNA interaction. Recent literatures emphasize the role of troxerutin (TXER) as an emerging anticancer agent. However, there are no reports on its intervention in any carcinogen-DNA interaction. The present study investigates the possibility of TXER, in prevention of 2-aminoanthracene (2-AA) contact with DNA. Steady state and time resolved fluorescence spectroscopy results, highlight the direct contact of 2-AA with DNA, while presence of TXER prevented this interaction. Gel-electrophoresis study clearly revealed that, TXER inhibits 2-AA+UVA radiation induced DNA damage. Fluorescence microscopic studies elucidated that, TXER treatment obstructs the 2-AA interaction with cellular DNA, while molecular docking showed the energetically favourable structure of TXER/2-AA/TXER complex. Further anti-mutagenicity experiment revealed that, TXER prevents the mutation induced colony formation in mutant strain of S. typhymurium. Our in vitro and ex vivo experimental findings provide imperative evidence about the protective role of TXER against environmental carcinogens through the inhibition of carcinogen-DNA interaction, implicating its potential for therapeutic applications in cancer.

Solanum torvum Swartz. fruit attenuates cadmium-induced liver and kidney damage through modulation of oxidative stress and glycosylation.

Increased levels of environmental pollutants are linked to almost all human disorders; the efficient method to manage the human health is through naturally available dietary molecule. Solanum torvum (ST) Swartz (Solanaceae) commonly called Turkey Berry is found in Africa, Asia, and South America. Its fruit, part of traditional Indian cuisine, is a widely consumed nutritious herb, acclaimed for its medicinal value. ST aqueous extract (STAe) (250, 500, and 1000 mg/kg b.w., 6 days; oral) against acute Cadmium (Cd) (6.3 mg/kg b.w., single dose; oral) toxicity was evaluated in rats. Protective effect was assessed using serum markers, tissue antioxidants, oxidant derivatives, glycoprotein, and histopathological studies. The activities of serum marker enzymes were increased (40-60 %); antioxidant enzymes such as SOD and CAT, GSH, and its metabolic enzyme activities were decreased (50-80 %) in the liver and kidney upon Cd intoxication. During STAe pre-treatment, at doses of 250 and 500 mg/kg b.w., the above changes were brought to near normal (25-63 %). Tissue 4-hydroxynonenal, 3-nitrotyrosine, and protein carbonyls were increased (8-15 fold) in Cd-alone-treated rats, whereas pre-supplementation of STAe significantly decreased their levels and inhibited the protein glycosylation effectively. The pharmacological effect of STAe was confirmed by histopathological observations. Based on previous literature and present investigation, we conclude that ST may serve as a potential functional food against environmental contaminant such as heavy metal-induced oxidative stress.

Probing the interaction of troxerutin with transfer RNA by spectroscopic and molecular modeling.

The studies on the interaction between tRNA (transfer RNA) and small molecules are an area of remarkable recent attention. For this notion a fundamental knowledge of the molecular features involving the interaction of small molecules with tRNA is crucial. Hence, in the present study we have investigated the interaction of TXER (troxerutin), natural bioflavonoid rutin derivative with yeast tRNA by using various spectroscopic techniques and molecular docking studies. The UV absorption and fluorescence emission studies demonstrated external binding of TXER on tRNA with low binding constant values as compared to strong binders. Circular dichroism (CD) spectroscopy study revealed that TXER did not show any significant modification on native conformation of tRNA. Furthermore in electrochemical study, the complex of TXER-tRNA did not expose any noticeable positive potential peak shift which indicated an interaction of TXER with tRNA by electrostatic or external binding mode. The docking study showed that the hydrogen and hydrophobic interactions were involved in binding of TXER-tRNA with docking score -7.0 kcal/mol. These findings led us to confirm the interaction of TXER on tRNA through external binding with low binding affinity, indicating its potential bioapplication in the future.

Spectroscopic and molecular docking studies on the interaction of troxerutin with DNA.

Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It possesses different biological activities in rising clinical world. The biological activity possessed by most of the drugs mainly targets on macromolecules. Hence, in the current study we have examined the interaction mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic methods, isothermal titration calorimetry (ITC) and molecular docking studies. Further, DNA cleavage study was carried out to find the DNA protection activity of TXER. UV-absorption and emission spectroscopy showed low binding constant values via groove binding. Circular dichroism study indicates that TXER does not modify native B-form of DNA, and it retains the native B-conformation. Furthermore, no effective positive potential peak shift was observed in TXER-DNA complex during electrochemical analysis by which it represents an interaction of TXER with DNA through groove binding. Molecular docking study showed thymine guanine based interaction with docking score -7.09 kcal/mol. This result was compared to experimental ITC value. The DNA cleavage study illustrates that TXER does not cause any DNA damage as well as TXER showed DNA protection against hydroxyl radical induced DNA damage. From this study, we conclude that TXER interacts with DNA by fashion of groove binding.

Green synthesis and characterization of selenium nanoparticles and its augmented cytotoxicity with doxorubicin on cancer cells.

Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of fenugreek seed extract. This method is capable of producing SeNPs in a size range of about 50-150 nm, under ambient conditions. The synthesized nanoparticles can be separated easily from the aqueous sols by a high-speed centrifuge. These selenium nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elemental analysis by X-ray fluorescence spectrometer (XRF). Nanocrystalline SeNPs were obtained without post-annealing treatment. FTIR spectrum confirms the presence of various functional groups in the plant extract, which may possibly influence the reduction process and stabilization of nanoparticles. The cytotoxicity of SeNPs was assayed against human breast-cancer cells (MCF-7). It was found that SeNPs are able to inhibit the cell growth by dose-dependent manner. In addition, combination of SeNPs and doxorubicin shows better anticancer effect than individual treatments.

Inhibition of hyaluronidase by N-acetyl cysteine and glutathione: role of thiol group in hyaluronan protection.

Hyaluronidase inhibitors have immense applications in pathophysiological conditions associated with hyaluronan-hyaluronidase system. The present study demonstrates the inhibitory efficacy of clinically accepted antioxidant N-acetyl cysteine (NAC) against hyaluronidase of serum, testis, and snake and bee venoms. The experimental and molecular dynamic simulation data suggest the non-competitive inhibition and involvement of thiol groups of both NAC and glutathione in exertion of inhibition. The bioavailability, less-toxic and antioxidant nature of NAC and glutathione could become valuable in the management of pathologies triggered by extracellular matrix degradation and to increase the endurance of hyaluronan based biomaterials/supplements, which are highly exciting aspects.

The extra cellular synthesis of gold and silver nanoparticles and their free radical scavenging and antibacterial properties.

The bio reduction of chloro auric acid (HAuCl(4)) and silver nitrate (AgNO(3)) is achieved extracellularly by using the aqueous extract of Solanum torvum (S. torvum) fruit. The nanoparticle formation was screened by UV-visible spectroscopy through color conversion due to surface plasma resonance bands at 560 nm and 430 nm for gold and silver nanoparticles respectively. The spherical shapes with smooth surface of gold and silver nanoparticles were analyzed through scanning electron microscope and its presence was confirmed by energy dispersive X-ray spectroscopy (SEM/EDX). The functional groups in the gold and silver salts and the bio interactive functional groups present in the S. torvum extract were characterized by employing Fourier transform infra-red spectroscopy (FTIR). The biomedical properties of gold and silver nanoparticles were premeditated as free radical scavenging activity and antibacterial static agents. Gold and silver nanoparticles serve as strong hydroxyl, superoxide, nitric oxide and DPPH radical scavengers in contrast to their corresponding metal oxides. The radical quenching properties of gold and silver nanoparticles were found to correlate with in vitro DNA protective effect. The silver nanoparticles show strong zone of inhibition against Escherichia coli, Pseudomonas and Bacillus whereas, gold nanoparticles exhibit fair zone of inhibition. To our knowledge this is the first report that S. torvum extract can reduce metal acids to nano materials.

Brassica nigra plays a remedy role in hepatic and renal damage.

CONTEXT: Black mustard [Brassica nigra (L.) Koch] of the Brassicaceae (Cruciferae) family is commonly used as a spice and a cheap source of antimicrobial agents for bacterial infections. OBJECTIVES: The present investigation was to demonstrate the protective effect of the methanol extract of B. nigra leaves against D-galactosamine (D-GalN)-induced hepatic and nephrotoxicity in Wistar rats. METHODS: Activity of the methanol extract of B. nigra at doses of 200 and 400 mg/kg b.wt. against D-GalN (500 mg/kg b.wt.) induced toxicity, with silymarin used as the standard. Histological damage, activities of serum marker enzyme, hematological changes, metabolites such as bilirubin, urea, uric acid, and creatinine levels, tissue thiobarbutric acid reactive substance, enzymic and non-enzymic antioxidants and inflammatory marker enzymes such as myeloperoxidase, cathepsin D, and acid phosphatase were assessed. RESULTS: The D-GalN-induced toxicity was evident from a significant increase (p < 0.001) in the serum and tissue inflammatory markers in toxic rats, when compared with the control (saline alone treated animals). The B. nigra pretreated groups (200 and 400 mg/kg b.wt.) showed significant (p < 0.001) reduction in the D-GalN-induced toxicity as obvious from biochemical parameters. Histopathological observations confirm the protective effect of B. nigra leaf extract by reduction in hepatic and renal tissue damage. Experimentals extract showed a similar effect as the standard. CONCLUSIONS: The crude methanol extract of B. nigra leaf lacks inherent toxicity and exhibits hepatic and nephroprotective effects against D-GalN-induced toxicity in Wistar rats.

Evaluation of antioxidant, radical scavenging activity and polyphenolics profile in Solanum torvum L. fruits.

UNLABELLED: Solanum torvum fruit widely used in traditional medicine of India and also in food preparation. Three different extracts such as water (WE), methanol (ME), and ethanol (EE) were used to evaluate their antioxidant and radical scavenging activity by different methods. All the assays results were compared with well-known standard antioxidants. The IC(50) values of assays were determined. The total phenolic and flavonoids content were found to be maximum in water and ethanol extracts, respectively. The electron quenching ability of fruit extract was assayed by DPPH and reducing power assays succeeding order were ME > EE > WE, respectively. Inhibition of membrane damage, was assayed interns of oxidative hemolysis and lipid peroxidation assays, among all WE extract shows 58.00% and 68.55 5% percentage of inhibition with 0.9 and 0.8 correlations (r(2)), respectively. Antioxidant and radical quenching efficiency were assayed by ß-carotene bleaching and hydroxyl radical scavenging method and results were compared with vitamin C and catechin. The in vitro free radical quenching and antioxidant results were well correlated with in vitro DNA protection assay. As analyzed by HPTLC gallic acid content is high in WE (1394 ± 25.0) and ME (598 ± 54.0) whereas ferulic acid is high in EE (32 ± 5.94) µg/g, respectively. This study indicate that S. torvum fruit is an excellent source of natural antioxidant and could be an effective nutritional food supplement, which interns will have therapeutic applications. PRACTICAL APPLICATION: In siddha medicine on the traditional systems of India the, ripened fruits are used in the preparation of tonic named as a "sundaivattaral choornam" is used to improve the health and prevent several diseases. This study has given an experimental evidence that S. torvum fruit is an excellent source of natural antioxidants.

Polyphenol contents and antioxidant activity of Brassica nigra (L.) Koch. leaf extract.

Profound research has been done on the medicinal value of Brassica nigra (BN) seeds, and the leaves of the plant have been investigated in this study. The methanol extracts of the leaves were subjected to several in vitro studies. The antioxidant activity of methanol extract was demonstrated with a wide range of concentration, 10-500 µg mL(-1), and the antioxidant activity increased with the increase in concentration. Total phenol content was found to be 171.73 ± 5.043 gallic acid equivalents and the total flavonoid content 7.45 ± 0.0945 quercetin equivalents. Further quantification and identification of the compounds were done by HPTLC and GC-MS analyses. The predominant phenolic compounds determined by HPTLC were gallic acid, followed by quercetin, ferulic acid, caffeic acid and rutin. The free radical quenching property of BN leaf extract suggests the presence of bioactive natural compounds.

Lactobacillus plantarum AS1 isolated from south Indian fermented food Kallappam suppress 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in male Wistar rats.

The relationship between antioxidant and anticancer properties of probiotic bacterium strain Lactobacillus plantarum AS1 (AS1) in colon cancer induced by 1,2-dimethylhydrazine (DMH) has been studied. In this study, an increased level of lipid peroxide (LPO) products and increased activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione-S transferase) and marker enzymes (alkaline phosphatase and acid phosphatase) in colon and plasma of cancer-bearing animals have been observed. AS1 was supplemented either before initiation or during initiation and selection/promotion phases of colon carcinogenesis and was found to be effective in altering lipid peroxidation and antioxidant enzyme activities and marker enzymes to a statistically significant level measured either in the colon and in the plasma. These alterations inclined towards normal in a time-dependent manner on AS1 supplementation. The mean tumor volume diameter and total number of tumors were found to be statistically decreased in AS1 pre- and post-treated rats. Furthermore, histopathological examination shows remarkable difference between control and treated groups. The in vitro antioxidant assay shows that AS1 has promising antioxidant property. These results demonstrate that AS1 strain can modulate the development of DMH-induced rat colon carcinogenesis through an antioxidant-dependent mechanism.

Identification, quantification of bioactive constituents, evaluation of antioxidant and in vivo acute toxicity property from the methanol extract of Vernonia cinerea leaf extract.

CONTEXT: Vernonia cinerea (L.) Less [Compositae (Asteraceae)] is used traditionally for several medical purposes such as inflammation, pain, fever, and cancer. OBJECTIVES: The present study identified the bioactive constituents in the methanol extract of Vernonia cinerea leaf and evaluated its antioxidant activity and acute toxicity. METHODS: The identification of phytochemicals was accomplished by GC-MS and the major antioxidant phenolic compounds in the extract were quantified by HPTLC analysis. To quantify the essential elements, atomic absorption spectrophotometeric analysis was carried out. Total phenol and flavonoid content was measured by Folin-Ciocalteau reagent and 2% aluminium chloride, respectively. RESULTS: GC-MS analysis identified the presence of 27 phytoconstituents. The predominant phenolic compound in the extract as quantified by HPTLC was gallic acid (1.92 mg/g) followed by rutin (0.705 mg/g), quercetin (0.173 mg/g), caffeic acid (0.082 mg/g) and ferulic acid (0.033 mg/g). The following elements were quantified: Fe (0.050 ppm), Mn (0.022 ppm), Co (0.0180 ppm), Pb (0.029 ppm), Hg (3.885 ppm) and Se (4.5240 ppm). The antioxidant activity of the extract increased with increasing concentration and the correlation (r²) for all in vitro assays were satisfactory. CONCLUSIONS: V. cinerea extract has significant (p < 0.05) antiradical activity. Hence, V. cinerea may have potential medicinal value and can be used in the formulation of pharmacological products for degenerative diseases.

Attenuation of the cardiac inflammatory changes and lipid anomalies by (-)-epigallocatechin-gallate in cigarette smoke-exposed rats.

Cigarette smoking is a major risk factor for cardiovascular diseases and exerts negative effects on the lipid profile. This study was aimed to evaluate the preventive role of (-)-epigallocatechin-gallate (EGCG) on lipid metabolism and cardiac inflammatory changes in cigarette smoke (CS) induced myocardial dysfunction. Adult male albino rats were exposed to side stream CS for a period of 12 weeks and simultaneously administered with EGCG (20 mg/kg b.w./day, p.o.). Exposure to CS showed significant increased (P < 0.05) activities of cardiac injury markers such as, creatine kinase-MB (CKMB) and lactate dehydrogenase (LDH) in serum and subsequent decrease in these enzyme activities in heart. A significant increase (P < 0.05) in serum total cholesterol, fatty acids, phospholipids, and triglycerides were observed in CS exposed rats, along with elevated low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol and decreased high density lipoprotein (HDL) cholesterol. In myocardium, total cholesterol, fatty acids and triglycerides were increased, whereas the phospholipids were found to be decreased. Cardiac lecithin: cholesterol acyl trasferase (LCAT), lipoprotein lipase (LPL), and plasma LCAT activities were significantly decreased (P < 0.05) on CS exposure. Supplementation of EGCG reverted the cardiac injury markers, abnormalities of lipid profile, and lipid-metabolizing enzymes in serum and myocardium. Western blot analysis showed a significant increase in protein expression levels of nuclear factor kappa-B (NF-κB), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in heart of CS exposed rats. EGCG-treated rats showed a significant decrease in the expression of inflammatory markers. Our data suggest that chronic CS causes lipidemic anomalies and cardiac inflammatory aberrations which may promote cardiac dysfunction and that the antioxidant EGCG exerts a cardio protective effect via reduction of oxidative stress.

Sodium selenite enhances glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital.

An element/compound that acts as an antioxidant as well as, can increase the oxidative stress offers a new approach in differentiation therapy. Experiments were carried out to determine the effect of selenite on DNA damage and glutathione peroxidase (GPx) activity in N-nitrosodiethylamine (DEN) induced, phenobarbital promoted rat hepatoma. Supra-nutritional level of selenite (4 ppm) was supplemented at either, before-initiation/after-initiation and/or during entire period of the study. At the end of experiment period (20 weeks), extent of DNA damage (alkaline comet assay), selenium concentration, and GPx activity were assessed on nodular tissue (NL) cells, surrounding liver (SL) cells, and whole liver tissue (control) cells. Hepatic selenium level and GPx activity were decreased in DEN and PB-administered animals, whereas the DNA damage was found to be increased in both NL and SL cells compared with control group. However, the DNA damage is more in SL cells than in NL cells. Pre-supplementation of selenite did not show any difference in DNA (strand breaks) damage, selenium, and GPx activity. Increased hepatic selenium concentration and GPx activity were observed in both NL and SL cells in post-supplementation and entire period of selenite supplemented animals compared to DEN + PB treated animals. However, DNA damage was increased in NL but decreased in SL cells. Supplementation of selenite alone for 16 or 20 weeks had shown increased DNA damage, selenium concentration, and GPx activity compared to normal control animals. In summary, cancer bearing animals increased DNA damage and decreased Se level and GPx activity in NL and SL cells and other organs in cancer bearing animals, supplementation of Se further provoked DNA damage (no change in pretreatment) in NL cells, however it decreased DNA damage SL cells and other organs (kidney, lungs, and spleen). On the other hand Se levels and GPx activity were increased in NL and SL cells and other organs of Se-supplemented rats (no difference in group 3 animals). These results demonstrate that, in addition to chemopreventive and chemotherapeutic role of selenite, it also prevents cellular DNA damage induced in cancerous condition.

Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice.

The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and anti-tumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC)--using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.

The inhibitory effect of sodium selenite on N-nitrosodiethylamine-induced and phenobarbital promoted liver tumourigenesis in rats based on the modulation of polyamine levels.

In the present study, we have evaluated the effects of dietary selenite (Se) on polyamine levels and its influence on N-nitrosodiethylamine (DEN) initiated and Phenobarbital (PB) promoted in rat liver carcinogenesis. Dietary selenite at a concentration of 4 ppm (through drinking water) was administered in rats either before initiation (4 weeks), or during promotion (16 weeks) and entire experimental period (20 weeks). Male Wistar strain of albino rats was treated with single intra peritoneal dose of DEN (200 mg kg(-1) body weight), after 2 weeks the carcinogenic effect was promoted by PB (0.05%; through diet). Alpha fetoprotein (AFP) was investigated after the 20th-week of experimental period. Selenite-treated animals markedly reduced the AFP during the time of pre-selenite [before initiation (4 weeks)] and entire experimental period (20 weeks), administration rather than the promotion period. This infers that anticancer property of selenite depends on the stage of carcinogenesis, rather than duration of treatment. Evaluation of polyamine levels in hepatoma and surrounding liver tissue showed significant difference in the selenite-treated groups compared with pair-fed control groups. Furthermore, histopathological examination showing remarkable difference between control and treated groups. These results demonstrate that selenite can modulate the development of DEN-induced and PB-promoted rat liver carcinogenesis through a polyamine-dependent mechanism.

Chemopreventive effect of piperine on mitochondrial TCA cycle and phase-I and glutathione-metabolizing enzymes in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.

Piperine is a major component of black (Piper nigrum Linn) and long pepper (Piper longum Linn) used widely in various systems of traditional medicine. We have evaluated the effect of piperine on mitochondrial tricarboxylic acid cycle and phase I and glutathione-metabolizing enzymes in Benzo(a)pyrene induced experimental lung carcinogenesis in swiss albino mice. Lung cancer bearing mice showed a significant decrease in the activities of mitochondrial enzymes-isocitrate dehydrogenase (ICDH), -ketoglutarate dehydrogenase (KDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and significantly increased NADPH-Cytochorome reductase (NADPH-C reductase), cytochrome P450 (cyt-p450) and cytochrome b5(cyt-b5). The activities of glutathione-metabolizing enzymes glutathione peroxidase(GPx), glutathione reductase (GR) and glucose-6-phospho dehydrogenase(G6PDH) were significantly lowered in lung-cancer bearing mice when compared with control mice. Piperine supplementation to tumour-induced animals significantly lowered the phase-I enzymes (NADPH-C reductase, cyt-p450 and cyt-b5)) and there was a rise in glutathione-metabolizing enzymes (GPx, GR and G6PDH), which indicated an antitumour and anti-cancer effect. Comparison of normal control mice and mice administered piperine only as drug control showed no significant variations in enzyme activities. Piprine administration to benzo(a)pyrene induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.

Response of human islets to isolation stress and the effect of antioxidant treatment.

The process of human islet isolation triggers a cascade of stressful events in the islets of Langerhans involving activation of apoptosis and necrosis and the production of proinflammatory molecules that negatively influence islet yield and function and may produce detrimental effects after islet transplantation. In this study, we showed that activation of nuclear factor-kappaB (NF-kappaB) and poly(ADP-ribose) polymerase (PARP), two of the major pathways responsible for cellular responses to stress, already occurs in pancreatic cells during the isolation procedure. NF-kappaB-dependent reactions, such as production and release of interleukin-6 and -8 and macrophage chemoattractant protein 1, were observed days after the isolation procedure in isolated purified islets. Under culture conditions specially designed to mimic isolation stress, islet proinflammatory responses were even more pronounced and correlated with higher islet cell loss and impaired secretory function. Here we present novel evidence that early interventions aimed at reducing oxidative stress of pancreatic cells and islets through the use of the catalytic antioxidant probe AEOL10150 (manganese [III] 5,10,15,20-tetrakis [1,3,-diethyl-2imidazoyl] manganese-porphyrin pentachloride [TDE-2,5-IP]) effectively reduces NF-kappaB binding to DNA, the release of cytokines and chemokines, and PARP activation in islet cells, resulting in higher survival and better insulin release. These findings support the concept that the isolation process predisposes islets to subsequent damage and functional impairment. Blocking oxidative stress can be beneficial in reducing islet vulnerability and can potentially have a significant impact on transplantation outcome.