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.

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.

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.

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.

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.

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.

Antioxidant-associated chemoprevention by sodium selenite in N-nitrosodiethylamine-induced and phenobarbital-promoted hepatocarcinogenesis in rats.

The anticarcinogenic/antioxidant potential of sodium selenite (Se), a micronutrient, was evaluated on liver tumourigenesis induced by N-nitrosodiethylamine (DEN) and promoted by phenobarbital (PB; 0.05% in diet). Male, albino rats of the Wistar strain were exposed intravenously to a single dose of DEN (200 mg x kg(-1) body weight). Se (4 ppm in drinking water) was supplemented before initiation, or during initiation and/or during the promotion period of carcinogenesis. At the end of 16 weeks (after DEN administration) nodular incidence, the total number of nodules and non-enzymic antioxidants such as vitamin E, vitamin C, total thiol, protein thiol and non-protein thiol contents were measured in hepatoma, surrounding tissue and kidney tissue of control and experimental groups. In hepatoma-bearing animals the above biochemical changes were decreased when compared with normal control animals. On Se treatment throughout the study, (20 weeks) the above biochemical changes reverted to normal levels. Pre- and post-treatment with Se also shows a tendency to reverse the above changes. The results indicate that prior application of Se significantly reverses the adverse changes produced during the tumourigenesis. Furthermore, prior applications of Se significantly reduced the cumulative number of tumours per tumour-bearing animals. The present study reveals the antitumour potential of Se against DEN-induced liver carcinogenesis.

Effect of dietary selenite on N-nitrosodiethylamine-induced and phenobarbital promoted multistage hepatocarcinogenesis in rat: reflection in some minerals.

Selenium (Se), a dietary micronutrient, plays a vital role in cancer chemotherapy in many organs including the liver. We have studied the relationship between some minerals, which are essential in normal functioning of cells and anticancer effect of Se in N-nitrosodiethylamine (DEN) induced and phenobarbital (PB) promoted multistage hepatocarcinogenesis. Se (4 ppm through drinking water; as sodium selenite) was given to animals throughout the study, before initiation and during promotion phase of hepatocarcinogenesis, in a defined experimental protocol. Se, sodium, potassium, calcium and iron were measured either in hepatoma, or surrounding liver tissue or whole liver tissue and serum of experimental animals. DEN and PB treatment significantly (P < 0.001) increased potassium, calcium and iron levels in serum, while it decreased (P < 0.001) the Se and sodium levels when compared with control rats. We have also observed significantly increased (P < 0.001) sodium, calcium and iron levels in hepatoma and surrounding liver tissue, whereas, Se, and potassium level was found to be decreased (P < 0.001) when compared with control rats. Supplementation of selenite throughout the study, before initiation and during promotion stage significantly alters the above mineral content. Results showed that the most significant beneficial effect of selenium during hepatocarcinogenesis was exerted potentially in long-term continuous and/or before the initiation phase of carcinogenicity, rather than in the promotion phase. The present and previous results from our laboratory suggest that sub-optimal intake of a single trace mineral can have broad effects on chemotherapy, providing a framework for understanding the multiple beneficial effects of selenium in cancer chemoprevention.

Stabilization of membrane bound enzyme profiles by sodium selenite in N-nitrosodiethylamine induced and phenobarbital promoted hepatocarcinogenesis in rats.

As part of a substantial effort to curtail the adverse health effects posed by hepatoma, studies have been conducted to elucidate the possible mechanism for the anticarcinogenic action of sodium selenite against N-nitrosodiethylamine induced hepatocarcinogenesis. Sodium selenite administered through drinking water at a dose of 4 ppm before initiation, or during initiation and/or during the promotion period of carcinogenesis exerted an in vivo stabilizing effect on cell membranes in rat hepatoma. This was demonstrated in normal rats and in animals whose biomembranes were rendered fragile by induction of hepatoma with N-nitrosodiethylamine and subsequent treatment with sodium selenite. The obtained results have shown a significant decrease in the activities of Na(+)/K(+)-ATPases, Mg(2+)-ATPases and Ca(2+)-ATPases (P < 0.001) in erythrocyte membrane; hepatoma and surrounding liver tissue and also erythrocyte membrane are more susceptible to lysis in cancer-bearing animals. The selenite administration reversed these adverse changes to near normal in selenite-treated animals. Such stabilization of biomembranes by selenite has a beneficial effect in the treatment of hepatoma and other cancers involving abnormal fragility of cell membrane. Previous evidence from this laboratory with respect to the anticancer potency of selenite against N-nitrosodiethylamine-induced hepatoma together with the present results suggests that potentially effective therapeutic protection can be achieved by pre-supplementation of selenite.

Influence of sodium selenite on glycoprotein contents in normal and N-nitrosodiethylamine initiated and phenobarbital promoted rat liver tumors.

Selenium in the form of sodium selenite is an essential micronutrient, that acts as an antioxidant/anticancer agent by its numerous macromolecules associated with them. This study emphasizes further evidence on its role as anticancer agent in experimental rats with N-nitrosodiethylamine (DEN) initiated (200 mg kg(-1) body weight) and phenobarbital (PB) promoted hepatoma. Serum, whole liver tissue (control animals, n=6), hepatoma and surrounding liver tissue samples from DEN-treated rats and rats supplemented with selenite (n=6) were collected. Total protein, albumin, globulin and albumin/globulin ratio were investigated. Hexose, hexosamine and sialic acid were also quantified. Animals treated with DEN resulted in significantly decreased levels of total protein, albumin and albumin/globulin ratio; on the other hand, globulin content was increased significantly when compared to control rats. We have also observed significant increased levels of hexose, hexosamine and sialic acid in serum, whole liver tissue (control), hepatoma and surrounding liver tissue of control and experimental animals. Supplementation of selenite (4 ppm) either before initiation, during initiation and/or during promotion stages alters the above biochemical changes significantly. Thus, supplementations of selenite in cancer bearing animals reduce the adverse changes that occur during cancer condition. However, the chemopreventive/chemotherapeutic effect of selenite is more pronounced when it was supplemented before and/or during initiation of cancer when compared to promotion stage. Our results emphasize the role of sodium selenite in cancer and strongly indicate its role as an essential micronutrient in cancer chemoprevention and therapy.

Sodium selenite modulates tumour marker indices in N-nitrosodiethylamine-initiated and phenobarbital-promoted rat liver carcinogenesis.

The effect of sodium selenite (Se) was investigated against two-stage rat liver carcinogenesis initiated by a single intraperitoneal injection of N-nitrosodiethylamine (DEN, 200 mg kg(-1) i.p.) followed by promotion with phenobarbital (PB, 0.05%) in a basal diet. Se (4 p.p.m.) was administered per os daily throughout the entire experiment, before the initiation, or during the promotion stage. The plasma, liver (hepatoma and surrounding tissue) and kidney tissue were investigated biochemically for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and 5'-nucleotidase. These enzyme activities were increased (p < 0.001) in plasma of hepatoma-bearing rats compared with normal control rats. The elevation of these enzyme activities in plasma was indicative of the persistent deteriorating effect of DEN in cancer-bearing animals. Aminotransferase levels were decreased in hepatoma and surrounding liver tissue, whereas lactate dehydrogenase, alkaline phosphatase and 5'-nucleotidase were increased in the cancer condition. These enzyme activities were reversed to near normal control values in animals treated with Se. It is apparent that the beneficial effect of Se is primarily exerted on the initiation phase and secondarily during the promotion stage of DEN-initiated rat liver carcinogenesis. The analysis of marker enzyme activities taken together with our previous findings clearly indicates the antitumour efficacy of sodium selenite on DEN-induced hepatoma animals.

Sodium selenite, dietary micronutrient, prevents the lymphocyte DNA damage induced by N-nitrosodiethylamine and phenobarbital promoted experimental hepatocarcinogenesis.

Selenium (Se), a micronutrient, has a long history in chemoprevention of mammary and colon cancers in rodent models. Se is a current clinical trial, having shown promise in prevention of prostate and other human cancers. The mechanisms involved in the in vivo anti-carcinogenic activity of Se remain to be elucidated. In the present study, we examined the effect of sodium selenite supplementation in lymphocytes, obtained from hepatoma bearing rats on DNA damage in correlation with oxidative stress. In addition, this study examined the supplementation of Se at 4-ppm levels in the form of sodium selenite either before initiation or during initiation and/or promotion phase's increases lymphocyte Se concentrations. This in turn improves lymphocyte resistance to oxidative stress and protection against the lymphocytes DNA damage. Supplementation of Se increased lymphocyte Se concentration and reduced lymphocytes DNA damage as determined by single cell gel electrophoresis. The enzymatic antioxidants such as superoxide dismutase, glutathione peroxidase, and catalase were found to be decreased while the thiobarbituric acid reactive substances level was increased in the lymphocytes of hepatoma bearing rats. Furthermore, the reactive oxygen species such as superoxide radicals and hydroxyl radicals were also found to be high in lymphocytes. Our present results explain the understanding of unique association between anti-peroxidative effect of Se and ultimately the capability of Se to prevent cancer.