Hepatoprotective potential of astaxanthin against 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured rat hepatocytes

The purpose of this study was to evaluate the effect of carotenoid astaxanthin (ASTA) on cultured primary rat hepatocytes treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT), lactate dehydrogenase (LDH) activity, 8-oxo-2-deoxyguanosine (8-OH-dG), total antioxidant capacity (TAC), and total oxidative stress (TOS) levels, and liver micronucleus rates. ASTA (2.5, 5, and 10 µM) was added to cultures alone or simultaneously with TCDD (5 and 10 µM) for 48 h. The results of MTT and LDH assays showed that both doses of TCDD caused significant decrease in cell viability. Also, TCDD significantly increased TOS and decreased TAC level in rat hepatocytes. On the basis of increasing doses, the dioxin caused significant increase in micronucleated hepatocytes) and 8-OH-dG level as compared to control culture. The presence of ASTA with TCDD minimized its effects on primary hepatocytes cultures and DNA damages.

[1]  M. Yousef,et al.  Beneficial effect of astaxanthin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced liver injury in rats , 2013, Toxicology and industrial health.

[2]  M. Yousef,et al.  Modulatory effect of l-glutamine on 2,3,7,8 tetrachlorodibenzo-p-dioxin-induced liver injury in rats , 2012, Toxicology and industrial health.

[3]  Q. Qian,et al.  Effect of Salvia miltiorrhiza Hydrophilic Extract on Antioxidant Enzymes in Diabetic Patients with Chronic Heart Disease: A Randomized Controlled Trial , 2012, Phytotherapy research : PTR.

[4]  F. Geyikoğlu,et al.  The Effect of Laurel Leaf Extract Against Toxicity Induced by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin in Cultured Rat Hepatocytes , 2011, Arhiv za higijenu rada i toksikologiju.

[5]  H. Hara,et al.  The Protective Effect and Action Mechanism of Vaccinium myrtillus L. on Gastric Ulcer in Mice , 2011, Phytotherapy research : PTR.

[6]  Á. Tósaki,et al.  Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen , 2011, Phytotherapy research : PTR.

[7]  F. Geyikoğlu,et al.  Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes , 2011, Cytotechnology.

[8]  B. P. Doctor,et al.  Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX. , 2011, Biochemical pharmacology.

[9]  J. T. Kim,et al.  Antioxidative effects of astaxanthin against nitric oxide-induced oxidative stress on cell viability and gene expression in bovine oviduct epithelial cell and the developmental competence of bovine IVM/IVF embryos. , 2010, Reproduction in domestic animals = Zuchthygiene.

[10]  M. Yousef,et al.  Propolis prevents aluminium-induced genetic and hepatic damages in rat liver. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  A. Fucic,et al.  Evaluation of the genotoxicity of 10 selected dietary/environmental compounds with the in vitro micronucleus cytokinesis-block assay in an interlaboratory comparison. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[12]  F. Gonzalez,et al.  Ube2l3 gene expression is modulated by activation of the aryl hydrocarbon receptor: implications for p53 ubiquitination. , 2010, Biochemical pharmacology.

[13]  R. Otton,et al.  Astaxanthin ameliorates the redox imbalance in lymphocytes of experimental diabetic rats. , 2010, Chemico-biological interactions.

[14]  Gokare A. Ravishankar,et al.  Characterization of microalgal carotenoids by mass spectrometry and their bioavailability and antioxidant properties elucidated in rat model. , 2010, Journal of agricultural and food chemistry.

[15]  R. Otton,et al.  Astaxanthin restores the enzymatic antioxidant profile in salivary gland of alloxan-induced diabetic rats. , 2010, Archives of oral biology.

[16]  Tung‐Kwang Lee,et al.  Radioprotective effect of American ginseng on human lymphocytes at 90 minutes postirradiation: a study of 40 cases. , 2010, Journal of alternative and complementary medicine.

[17]  F. Geyikoğlu,et al.  Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood , 2010, Cytotechnology.

[18]  D. El-Agamy,et al.  Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits , 2010, Archives of pharmacal research.

[19]  D. Marin,et al.  Astaxanthin addition improves human neutrophils function: in vitro study , 2010, European journal of nutrition.

[20]  T. Zacharewski,et al.  PCB153-elicited hepatic responses in the immature, ovariectomized C57BL/6 mice: comparative toxicogenomic effects of dioxin and non-dioxin-like ligands. , 2010, Toxicology and applied pharmacology.

[21]  D. Marin,et al.  Astaxanthin prevents in vitro auto-oxidative injury in human lymphocytes , 2010, Cell Biology and Toxicology.

[22]  B. Chew,et al.  Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans , 2010, Nutrition & metabolism.

[23]  D. Schrenk,et al.  Inhibition of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin depends on protein biosynthesis , 2010, Cell Biology and Toxicology.

[24]  L. Skibsted,et al.  Fast regeneration of carotenoids from radical cations by isoflavonoid dianions: importance of the carotenoid keto group for electron transfer. , 2010, The journal of physical chemistry. A.

[25]  T. Hibi,et al.  An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. , 2010, World journal of gastroenterology.

[26]  N. Demir,et al.  Effect of astaxanthin on hepatocellular injury following ischemia/reperfusion. , 2010, Toxicology.

[27]  I. Nishigaki,et al.  Cytoprotective role of astaxanthin against glycated protein/iron chelate‐induced toxicity in human umbilical vein endothelial cells , 2010, Phytotherapy research : PTR.

[28]  H. Shertzer Protective Effects of the Antioxidant 4b,5,9b,10-Tetrahydroindeno[1,2-b]indole Against TCDD Toxicity in C57BL/6J Mice , 2010, International journal of toxicology.

[29]  F. Tinahones,et al.  Assessment of cellular and plasma oxidative stress in SAHS patients before and after continuous positive airway pressure treatment. , 2010, Clinical laboratory.

[30]  G. Sudhandiran,et al.  Astaxanthin inhibits tumor invasion by decreasing extracellular matrix production and induces apoptosis in experimental rat colon carcinogenesis by modulating the expressions of ERK-2, NFkB and COX-2 , 2011, Investigational New Drugs.

[31]  M. Kojima,et al.  Effect of 5-S-GAD on UV-B-induced cataracts in rats , 2009, Japanese Journal of Ophthalmology.

[32]  H. Takagi,et al.  Metabolic Engineering of Saccharomyces cerevisiae for Astaxanthin Production and Oxidative Stress Tolerance , 2009, Applied and Environmental Microbiology.

[33]  M. Hayashi,et al.  Evaluation of a liver micronucleus assay with 12 chemicals using young rats (II): a study by the Collaborative Study Group for the Micronucleus Test/Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. , 2008, Mutagenesis.

[34]  Z. Punja,et al.  Transgenic carrot plants accumulating ketocarotenoids show tolerance to UV and oxidative stresses. , 2008, Plant physiology and biochemistry : PPB.

[35]  F. Ünal,et al.  Genotoxic action of fungicide Conan 5FL (Hexaconazole) on mammalian cells in vivo and in vitro , 2008 .

[36]  P. Lin,et al.  2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress, DNA strand breaks, and poly(ADP-ribose) polymerase-1 activation in human breast carcinoma cell lines. , 2007, Toxicology letters.

[37]  Gokare A. Ravishankar,et al.  Stabilization of astaxanthin in edible oils and its use as an antioxidant. , 2007 .

[38]  R. Mehta,et al.  Modulating effects of dietary fats on methylmercury toxicity and distribution in rats. , 2007, Toxicology.

[39]  Brock Chittim,et al.  Comparative toxicogenomic analysis of the hepatotoxic effects of TCDD in Sprague Dawley rats and C57BL/6 mice. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[40]  H. Sesso Carotenoids and cardiovascular disease: what research gaps remain? , 2006, Current opinion in lipidology.

[41]  F. Geyikoğlu,et al.  Protective effect of sodium selenite on genotoxicity to human whole blood cultures induced by aflatoxin B1 , 2005 .

[42]  Maria Teresa Landi,et al.  Handling of dioxin measurement data in the presence of non-detectable values: overview of available methods and their application in the Seveso chloracne study. , 2005, Chemosphere.

[43]  A. Hanberg,et al.  Gastric hamartomatous tumours in a transgenic mouse model expressing an activated dioxin/Ah receptor. , 2005, Anticancer research.

[44]  H. Chang,et al.  Suppressive Effect of Astaxanthin Isolated from the Xanthophyllomyces dendrorhous Mutant on Ethanol-Induced Gastric Mucosal Injury in Rats , 2005, Bioscience, biotechnology, and biochemistry.

[45]  Hue Lee,et al.  Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes. , 2005, Journal of biomedical science.

[46]  L. Needham,et al.  Developmental Dental Aberrations After the Dioxin Accident in Seveso , 2004, Environmental health perspectives.

[47]  E. Röhrdanz,et al.  Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity. , 2003, Toxicology.

[48]  Y. Fujii‐Kuriyama,et al.  Functional role of AhR in the expression of toxic effects by TCDD. , 2003, Biochimica et biophysica acta.

[49]  A. Westwell,et al.  The aryl hydrocarbon receptor in anticancer drug discovery: friend or foe? , 2002, Current pharmaceutical design.

[50]  H. Friess,et al.  Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer , 2002, Oncogene.

[51]  Xiao-chao Ma,et al.  Cytotoxicity of flutamide and 2-hydroxyflutamide and their effects on CYP1A2 mRNA in primary rat hepatocytes. , 2002, Acta pharmacologica Sinica.

[52]  P. Pemberton,et al.  Oxidative stress in chronic hepatitis C: not just a feature of late stage disease. , 2002, Journal of hepatology.

[53]  K. Fukuzawa,et al.  Molecular characteristics of astaxanthin and beta-carotene in the phospholipid monolayer and their distributions in the phospholipid bilayer. , 2001, Chemistry and physics of lipids.

[54]  N. Nishimura,et al.  Induction of metallothionein in the livers of female Sprague-Dawley rats treated with 2,3,7 ,8-tetrachlorodibenzo-p-dioxin. , 2001, Life sciences.

[55]  L. Robertson,et al.  Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress. , 2001, Biochemical pharmacology.

[56]  S. Kim,et al.  Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and antioxidative enzymes in the liver of CCl4-treated rats. , 2001, Methods and findings in experimental and clinical pharmacology.

[57]  S. Stohs,et al.  The relative abilities of TCDD and its congeners to induce oxidative stress in the hepatic and brain tissues of rats after subchronic exposure. , 2000, Toxicology.

[58]  M. DeVito,et al.  Oxidative stress in female B6C3F1 mice following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[59]  K. Iijima,et al.  Intervention of astaxanthin against cyclophosphamide ‐ induced oxidative stress and DNA damage : a study in mice , 2010 .

[60]  M. Lagarde,et al.  Protective effect of docosahexaenoic acid against hydrogen peroxide-induced oxidative stress in human lymphocytes. , 1999, Biochemical pharmacology.

[61]  G. Lescoat,et al.  Bgugaine, a pyrrolidine alkaloid from Arisarum vulgare, is a strong hepatotoxin in rat and human liver cell cultures. , 1999, Toxicology letters.

[62]  D. Nebert,et al.  Dioxin causes a sustained oxidative stress response in the mouse. , 1998, Biochemical and biophysical research communications.

[63]  F. Ridolfi,et al.  Fibrogenic effect of oxidative stress on rat hepatic stellate cells , 1998, Hepatology.

[64]  P. Kidd Glutathione: Systemic Protectant Against Oxidative and Free Radical Damage Dedicated to the memory of Professor Daniel Mazia, my PhD mentor and a pioneer in cell biology , 2000 .

[65]  M. Gross,et al.  Immunomodulating actions of carotenoids: enhancement of in vivo and in vitro antibody production to T-dependent antigens. , 1994, Nutrition and cancer.

[66]  Q. Pye,et al.  Methylene blue and rose bengal photoinactivation of RNA bacteriophages: comparative studies of 8-oxoguanine formation in isolated RNA. , 1993, Archives of biochemistry and biophysics.

[67]  N. Krinsky,et al.  Astaxanthin and canthaxanthin are potent antioxidants in a membrane model. , 1992, Archives of biochemistry and biophysics.

[68]  B. Halliwell,et al.  Role of free radicals and catalytic metal ions in human disease: an overview. , 1990, Methods in enzymology.

[69]  K. Utsumi,et al.  Inhibition of oxidative injury of biological membranes by astaxanthin. , 1990, Physiological chemistry and physics and medical NMR.

[70]  B. Halliwell,et al.  Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. , 1986, Archives of biochemistry and biophysics.

[71]  R. Floyd,et al.  Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation. , 1986, Free radical research communications.