Naringin Inhibits Tumor Growth And Reduces Interleukin-6 And Tumor Necrosis Factor α Levels In Rats With Walker 256 Carcinosarcoma

The flavonoid naringin is a polyphenolic compound that naturally occurs in citrus. Patients with cancer generally present features of malnutrition and cachexia. Levels of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) are raised in patients with cancer. This study was designed to analyze the in vivo effect of naringin in the therapeutic treatment of rats bearing Walker 256 carcinosarcoma (W256). Rats were treated intraperitoneally with different doses of naringin (10, 25 and 35 mg/kg), for 50 days. At 25 mg/kg, naringin inhibited tumor growth by ∼75%. With this treatment, TNF-α and IL-6 levels decreased (p3.0.CO;2-NSkipworth, R.J.E., Stewart, G.D., Dejong, C.H.C., Preston, T., Fearon, K.C.H., Pathophysiology of cancer cachexia: Much more than host-tumour interaction? (2007) Clinical Nutrition, 26 (6), pp. 667-676. , DOI 10.1016/j.clnu.2007.03.011, PII S0261561407000696Seruga, B., Zhang, H., Bernstein, L.J., Tannock, I.F., Cytokines and their relationship to the symptoms and outcome of cancer (2008) Nat Rev Cancer, 8, pp. 887-899Tisdale, M.J., Metabolic abnormalities in cachexia and anorexia (2000) Nutrition, 16, pp. 1013-1014Tisdale, M.J., Mechanisms of cancer cachexia (2009) Physiol Rev, 89, pp. 381-410Argiles, J.M., Busquets, S., Felipe, A., Lopez-Soriano, F.J., Molecular mechanisms involved in muscle wasting in cancer and ageing: Cachexia versus sarcopenia (2005) International Journal of Biochemistry and Cell Biology, 37 (5 SPEC. ISS.), pp. 1084-1104. , DOI 10.1016/j.biocel.2004.10.003Tang, M.X., Ogawa, K., Asamoto, M., Hokaiwado, N., Seeni, A., Suzuki, S., Takahashi, S., Shirai, T., Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells (2007) Cancer Science, 98 (4), pp. 471-477. , DOI 10.1111/j.1349-7006.2007.00417.xLimtrakul, P., Phromnoi, K., Reuter, S., Sung, B., Aggarwal, B.B., A dihydroxy-pentamethoxyflavone from Gardenia obtusifolia suppresses proliferation and promotes apoptosis of tumor cells through modulation of multiple cell signaling pathways (2010) Anticancer Res, 30, pp. 3599-3610Ribeiro, I.A., Ribeiro, M.H.L., Naringin and naringenin determination and control in grapefruit juice by a validated HPLC method (2008) Food Control, 19 (4), pp. 432-438. , DOI 10.1016/j.foodcont.2007.05.007, PII S0956713507001077Ye, H., Xu, H.D., Yu, C.G., Dai, Y.J., Liu, G.Y., Xu, W.P., Yuan, S., Hydroxylation of naringin by Trichoderma harzianum to dramatically improve its antioxidative activity (2009) Enzyme Microb Tech, 45, pp. 282-287Han, S.-S., You, I.-J., Studies on antimicrobial activities and safety of natural naringin in Korea (1988) Korean Soc Mycol, 16, pp. 33-40Kaul, T.N., Middleton Jr., E., Ogra, P.L., Antiviral effect of flavonoids on human viruses (1985) Journal of Medical Virology, 15 (1), pp. 71-79. , DOI 10.1002/jmv.1890150110Martin, M.J., Marhuenda, E., Perez-Guerrero, C., Franco, J.M., Antiulcer effect of naringin on gastric lesions induced by ethanol in rats (1994) Pharmacology, 49 (3), pp. 144-150Kanno, S.-I., Tomizawa, A., Hiura, T., Osanai, Y., Shouji, A., Ujibe, M., Ohtake, T., Ishikawa, M., Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice (2005) Biological and Pharmaceutical Bulletin, 28 (3), pp. 527-530. , DOI 10.1248/bpb.28.527So, F.V., Guthrie, N., Chambers, A.F., Moussa, M., Carroll, K.K., Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices (1996) Nutrition and Cancer, 26 (2), pp. 167-181Le, M.L., Murphy, S.P., Hankin, J.H., Wilkens, L.R., Kolonel, L.N., Intake of flavonoids and lung cancer (2000) Journal of the National Cancer Institute, 92 (2), pp. 154-160Tomasik, P., (2004) Chemical and Functional Properties of Food Saccharides, , Boca Raton: CRC PressBenavente-Garcia, O., Castillo, J., Update on uses and properties of citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity (2008) J Agric Food Chem, 56, pp. 6185-6205Kawaguchi, K., Kikuchi, S., Hasegawa, H., Maruyama, H., Morita, H., Kumazawa, Y., Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin (1999) European Journal of Pharmacology, 368 (2-3), pp. 245-250. , DOI 10.1016/S0014-2999(98)00867-X, PII S001429999800867XGordon, P.B., Holen, I., Seglen, P.O., Protection by naringin and some other flavonoids of hepatocytic autophagy and endocytosis against inhibition by okadaic acid (1995) J Biol Chem, 270, pp. 5830-5838Camargo, C.A., Da Silva, M.E., Da Silva, R.A., Justo, G.Z., Gomes-Marcondes, M.C., Aoyama, H., Inhibition of tumor growth by quercetin with increase of survival and prevention of cachexia in Walker 256 tumor-bearing rats (2011) Biochem Biophys Res Commun, 406, pp. 638-642Vale, C., Stewart, L., Tierney, J., Trends in UK cancer trials: Results from the UK Coordinating Committee for Cancer Research National Register of Cancer Trials (2005) British Journal of Cancer, 92 (5), pp. 811-814. , DOI 10.1038/sj.bjc.6602425Gomes-Marcondes, M.C.C., Honma, H.N., Areas, M.A., Cury, L., Effect of Walker 256 tumor growth on intestinal absorption of leucine, methionine and glucose in newly weaned and mature rats (1998) Brazilian Journal of Medical and Biological Research, 31 (10), pp. 1345-1348Gomes-Marcondes, M.C., (1994) Influência Da Gestação Sobre O Crescimento Do Câncer e Deste Sobre O Desenvolvimento Fetoplacentário, , Campinas, São Paulo, Brazil: Universidade Estadual de Campinas (UNICAMP), PhD ThesisKaplan, E.L., Meier, P., Nonparametric-estimation from incomplete observations (1958) J Am Stat Assoc, 53, pp. 457-481Mantel, N., Evaluation of survival data and two new rank order statistics arising in its consideration (1966) Cancer Chemother Rep, 50, pp. 163-170Cox, D.R., Regression models and life-tables (1972) J Roy Stat Soc, 34, pp. 187-1120Kawakami, M., Pekala, P.H., Lane, M.D., Cerami, A., Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells (1982) Proceedings of the National Academy of Sciences of the United States of America, 79 (3 I), pp. 912-916Busquets, S., Deans, C., Figueras, M., Moore-Carrasco, R., Lopez-Soriano, F.J., Fearon, K.C.H., Argiles, J.M., Apoptosis is present in skeletal muscle of cachectic gastro-intestinal cancer patients (2007) Clinical Nutrition, 26 (5), pp. 614-618. , DOI 10.1016/j.clnu.2007.06.005, PII S0261561407001069Inui, A., Cancer anorexia-cachexia syndrome: Are neuropeptides the key? (1999) Cancer Res, 59, pp. 4493-4501Samuels, S.E., Knowles, A.L., Tilignac, T., Debiton, E., Madelmont, J.C., Attaix, D., Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice (2000) Cancer Res, 60, pp. 4968-497

Hepatoprotective Effect Of Arctium Lappa Root Extract On Cadmium Toxicity In Adult Wistar Rats

This study was performed to determine the effects of Arctium lappa (Al) to protect against cadmium damage in the rat liver. Male rats received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) with or without Al extract administered daily by gavage (300 mg/kg BW) for 7 or 56 days. After 7 days, Al caused plasma transaminase activity to diminish in groups Al (glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) and CdAl (GPT). After 56 days, GOT and GPT plasma activities were reduced in the Cd group. No alteration in plasma levels of creatinine, total bilirubin, and total protein were observed. GOT liver activity increased in the Cd group. No alteration was observed in superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and malondialdehyde (MDA) dosage. In the Cd group, hepatocyte proportion decreased and sinusoid capillary proportion increased. In the Al and CdAl groups, the nuclear proportion increased and the cytoplasmic proportion decreased. The hepatocyte nucleus density reduced in Cd and increased in the Al group. After 56 days, there was no alteration in the Cd group. In Al and CdAl groups, the nuclear proportion increased without cytoplasmic proportion variation, but the sinusoid capillary proportion was reduced. The hepatocyte nucleus density decreased in the Cd group and increased in the Al and CdAl groups. In conclusion, the liver function indicators showed that A. lappa protected the liver against cadmium toxicity damage. © 2014 Springer Science+Business Media.1602250257Radosavljević, T., Mladenović, D., Ninković, M., Vučević, D., Boričić, I., Ješić- Vukićević, R., Šljivančanin, T., Todorović, V., Oxidative stress in rat liver during acute cadmium and ethanol intoxication (2012) J Serb Chem Soc, 77, pp. 159-176Vicente-Sánchez, C., Egido, J., Sánchez-González, P.D., Pérez-Barriocanal, F., López-Novoa, J.M., Morales, A.I., Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity (2008) Food Chem Toxicol, 46, pp. 2279-2287Jihen, E.H., Imed, M., Fatima, H., Abdelhamid, K., Protective effects of selenium and zinc on cadmium (Cd) toxicity in the liver and kidney of the rat: Histology and Cd accumulation (2008) Food Chem Toxicol, 46, pp. 3522-3527Matović, V., Buha, A., Bulat, Z., Dukić-Ćosić, D., Miljković, M.I., Ivaniševic, J., Kotur-Stevuljevic, J., Route-dependent effects of cadmium/cadmiumand magnesium acute treatment on parameters of oxidative stress in rat liver (2012) Food Chem Toxicol, 50, pp. 552-557Baba, H., Tsuneyama, K., Yazaki, M., Nagata, K., Minamisaka, T., Tsuda, T., Nomoto, K., Imura, J., The liver in itai-itai disease (chronic cadmium poisoning): Pathological features and metallothionein expression (2013) Mod Pathol, 26, pp. 1-7El-Sokkary, G.H., Nafady, A.A., Shabash, E.H., Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat (2009) Ecotoxicol Environ Saf, 73, pp. 456-463Lin, C.C., Lin, J.M., Yang, J.J., Chuang, S.C., Ujiie, T., Anti-inflammatory and radical scavenge effects of Arctium lappa (1996) Amer J Chin Med, 24, pp. 127-138Lin, S., Chung, T., Lin, C., Ueng, T.H., Lin, Y., Lin, S., Wang, L., Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage (2000) Amer J Chin Med, 28, pp. 163-174Lin, S.C., Lin, C.H., Lin, Y.H., Chen, C.F., Chen, I.C., Wang, L., Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride (2002) J Biomed Sci, 9, pp. 401-409Predes, F.S., Ruiz, A.L.T.G., Carvalho, J.E., Foglio, M.A., Dolder, H., Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts (2011) BMC Complement Altern Med, 11, pp. 25-30Cohen, G., Dembiec, D., Marcus, J., Measurement of catalase activity in tissue extracts (1970) Anal Biochem, 34, pp. 30-38Tang, B., Wang, Y., Chen, Z., Catalytic spectrofluorimetric determination of superoxide anion radical and superoxide dismutase activity using N, N-dimethylaniline as the substrate for horseradish peroxidase (HRP) (2002) Spectrochim Acta Part a, 58, pp. 2557-2562Habig, W.H., Pabst, M.J., Jakoby, W.B., Glutathione S-transferases: The first enzymatic step in mercapturic acid formation (1970) J Biol Chem, 249, pp. 7130-7139Uchiyama, M., Mihara, M., Determination of malonaldehyde precursor in tissues by thiobarbituric acid test (1978) Analytical Biochemistry, 86 (1), pp. 271-278Predes, F.S., Diamante, M.A.S., Dolder, H., Testis response to two low doses of cadium in Wistar rats (2010) Int J Exp Pathol, 91, pp. 125-131Ashafa, A.O.T., Yakubu, M.T., Grierson, D.S., Afolayan, A.J., Effects of aqueous extract from the leaves of Chrysocoma ciliata L. on some biochemical parameters of Wistar rats (2009) Afr J Biotechnol, 8, pp. 1425-1430Mani, U., Prasad, A.K., Suresh, K.V., Lal, K., Kanojia, R.K., Chaudhari, B.P., Murthy, R.C., Effect of fly ash inhalation on biochemical and histomorphological changes in rat liver (2007) Ecotoxicology and Environmental Safety, 68 (1), pp. 126-133. , DOI 10.1016/j.ecoenv.2006.10.013, PII S0147651306002107Kang, M.Y., Cho, S.H., Lim, Y.H., Seo, J.C., Hong, Y.C., Effects of environmental cadmium exposure on liver function in adults (2013) Occup Environ Med, 70, pp. 268-273Nemmiche, S., Chabane-Sari, D., Guiraud, P., Role of alpha-tocopherol in cadmium-induced oxidative stress in Wistar rat's blood, liver and brain (2007) Chemico-Biological Interactions, 170 (3), pp. 221-230. , DOI 10.1016/j.cbi.2007.08.004, PII S0009279707002608Borges, L.P., Brandão, R., Godoi, B., Nogueira, C.W., Zeni, G., Oral administration of diphenyl diselenide protects against cadmium-induced liver damage in rats (2008) Chem Biol Interact, 171, pp. 15-25Renugadevi, J., Prabu, S.M., Naringenin protects against cadmium-induced oxidative renal dysfunction in rats (2010) Toxicology, 256, pp. 128-134Tzirogiannis, K.N., Panoutsopoulos, G.I., Demonakou, M.D., Hereti, R.I., Alexandropoulou, K.N., Basayannis, A.C., Mykoniatis, M.G., Time-course of cadmium-induced acute hepatotoxicity in the rat liver: The role of apoptosis (2003) Archives of Toxicology, 77 (12), pp. 694-701. , DOI 10.1007/s00204-003-0499-yKoyu, A., Gokcimen, A., Ozguner, F., Bayram, D.S., Kocak, A., Evaluation of the effects of cadmium on rat liver (2006) Molecular and Cellular Biochemistry, 284 (1-2), pp. 81-85. , DOI 10.1007/s11010-005-9017-2Rikans, L., Yamano, T., Mechanisms of cadmium-mediated acute hepatotoxicity (2000) J Biochem Mol Toxicol, 14, pp. 110-11

Erratum To: Hepatoprotective Effect Of Arctium Lappa Root Extract On Cadmium Toxicity In Adult Wistar Rats (biological Trace Element Research (2014) 160, (250-257) Doi: 10.1007/s12011-014-0040-6)

[No abstract available]160345