A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats

スポンサーリンク

概要

• 論文の詳細を見る

• A chronic toxicity study of kojic acid (KA) was performed using male F344 rats by dietary administration at concentrations of 0 (control), 0.5 and 2.0% for 55 weeks. Body weight gain was suppressed in the 2.0% group. The major hematological findings were decreased red blood cell (RBC) count and hematocrit (Ht) values at both 0.5 and 2.0%. In serum biochemistry, increased aspartate transaminase (AsT), alanine transaminase (AlT), alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GTP) levels were detected in the 0.5 and 2.0% groups. Histopathologically, single cell necrosis of hepatocytes and proliferation of bile ductules in both treatment groups, and hypertrophy of hepatocytes, granulomas and proliferation of bile ducts in the 2.0% group were increased in incidence, and numbers and areas of glutathione-S-transferase placental-form (GST-P) positive foci were increased in the liver of the 2.0% group. In the thyroids, diffuse follicular cell hyperplasia at 0.5 and 2.0% and focal follicular cell hyperplasia and follicular adenoma at 2.0% were increased. A thyroid follicular carcinoma was also observed at 2.0%. Additionally, increased incidences of hyaline casts and basophilic tubules in the kidneys at 2.0% and microgranulomas containing crystals in the lung in both treatment groups were noted. At 2.0%, hypertrophy of cortical cells in zona fasciculata was also increased in the adrenals. In conclusion, no observed adverse effect level of KA was below 0.5%, which is equivalent to 227mg/kg body weight/day in male rats.

• 2009-06-01

著者

• Ota Yoshio

  Division of Pathology, National Institute of Health Sciences

• Imai Toshio

  Division of Pathology, National Institute of Health Sciences

• Onose Jun-ichi

  Division of Pathology, National Institute of Health Sciences

• Takami Shigeaki

  Division of Pathology, National Institute of Health Sciences

• Cho Young-Man

  Division of Pathology, National Institute of Health Sciences

• Hirose Masao

  Division of Pathology, National Institute of Health Sciences

• Nishikawa Akiyoshi

  Division of Pathology, National Institute of Health Sciences

• Mori H

  Division Of Pathology National Institute Of Health Sciences

• Hirose Masao

  国立医薬品食品衛生研究所 病理

• Hirose M

  Division Of Pathology National Institute Of Health Sciences:food Safety Commission

• Hirose Masao

  国立医薬品食品衛生研究所 病理部

• Hirose Masao

  名古屋市立大学 医学研究科実験病態病理学

• Cho Young-man

  Division Of Pathology National Institute Of Health Sciences

• Cho Young-man

  国立医薬品食品衛生研究所 病理部

• Hoshi Manabu

  大阪市立大学 医学部病理学

• Mori Hideki

  岐阜薬科大学 生物薬学研究所

• Makita Hiroki

  岐阜大学 第1病理

• Onose Jun-ichi

  Division Of Pathology National Institute Of Health Sciences

• Onose Jun-ichi

  Division Of Biochemistry And Immunochemistry National Institute Of Health Sciences

• Hirose Masao

  Division Of Pathology National Institute Of Health Sciences

• Hirose Masao

  Div. Pathol. Natl. Inst. Htlh. Sci.

• 今井 淑夫

  Division Of Pathology National Institute Of Health Sciences

• 今井 淑夫

  東京工業大学部有機材科工学科

• Hirota M

  Department Of Bioscience And Biotechnology Faculty Of Agriculture Shinshu University

• 今井 淑夫

  元 東京工業大学工学部有機材料工学科

• Imai Yoichiro

  Department Of Clinical Biochemistry Fujita Health University College

• Nishikawa A

  Div. Of Pathology National Inst. Of Health Sciences

• Nishikawa Akiyoshi

  Division Of Pathology Biology Safety Research Center National Institute Of Health Sciences

• Nishikawa A

  National Inst. Health Sci. Tokyo Jpn

• Hosono M

  Aburahi Laboratories Shionogi Research Laboratories Shionogi Co Ltd.

• Nishikawa A

  National Institute Of Health Science Osaka Branch National Institute Of Health Sciences

• Mori Hideki

  College Of Engineering Graduate School Of Osaka Prefecture University

• Hirose Masao

  Department Of Pathology Nagoya Higashi Municipal Hospital

• Ota Yoshio

  Division Of Pathology National Institute Of Health Sciences

• 今井 淑夫

  東京工業大学

• Takami Shigeaki

  Division Of Pathology National Institute Of Health Sciences

• Mori Hideki

  First Department Of Pathology Gifu University School Of Medicine

• Imai Toshio

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• Nishikawa Akiyoshi

  Division Of Pathology Nihs

関連論文

• A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats
• Increased H-ras mutation frequency in mammary tumors of rats initiated with N-methyl-N-nitrosourea (MNU) and treated with acrylamide
• Lack of modifying effects of prepubertal exposure to acrylamide (AA) on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis in F344 rats
• Enhancement of esophageal carcinogenesis in acid reflux model rats treated with ascorbic acid and sodium nitrite in combination with or without initiation
• Inhibitory Effects of Octreotide Acetate, a Somatostatin Analog, on Spontaneous Chronic Pancreatitis in WBN/Kob Rats
• Rapid Screening for Chemopreventive Agents in Herbal Extracts in a PhIP Rat Model with DNA Adduct and Cell Proliferation as End-Points
• DNA Adduct Formation, Nucleolar Segregation and Cell Proliferation in Rats Treated with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
• Depression of T cell-mediated immunity reduces sulfadimethoxine-induced capsular inflammation and inhibits associated development of invasive thyroid follicular cell carcinomas in rats
• Lack of enhancement of susceptibility to mammary and thyroid carcinogenesis in rats exposed to DMBA and DHPN following prepubertal iodine deficiency
• In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys of rats given potassium bromate
• Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
• Comparison of enhancing effects of different goitrogen treatments in combination with β-estradiol-3-benzoate for establishing a rat two-stage thyroid carcinogenesis model to detect modifying effects of estrogenic compounds
• In vivo mutagenicity and oxidative DNA damage in the livers of gpt delta mice treated with flumequine(Mutagenicity, Carcinogenicity, Proceedings of the 32nd Annual Meeting)
• Lack of Modifying Effects of Combined Treatment of t-butylhydroquinone and Sodium Nitrite on Forestomach Carcinogenesis in rasH2 Mice Initiated with N-ethyl-N-nitrosourea
• Lack of Initiating Activity of Kojic Acid on Hepatocarcinogenesis in F344 Rats
• Tumorigenic Susceptibility of Catechol on the Gastric Mucosa in rasH2 Mice
• Lack of Modifying Effect of Glycerol in Pulmonary Carcinogenesis in rasH2 Mice Induced by Urethane or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
• LACK OF MODIFYING EFFECTS OF EUGENOL ON DEVELOPMENT OF LUNG PROLIFERATIVE LESIONS INDUCED BY URETHANE IN TRANS-GENIC MICE CARRYING THE HUMAN PROTOTYPE c-Ha-ras GENE
• Lack of Modifying Effects of Cinnamaldehyde on Development of Lung Proliferative Lesions Induced by Urethane in Transgenic Mice Carrying the Human Prototype c-Ha-ras Gene
• Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
• Roles of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and β-catenin activation in gastric carcinogenesis in N-methyl-N-nitrosourea-treated K19-C2mE transgenic mice
• Inhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori-associated gastric carcinogenesis in Mongolian gerbils
• Lack of a Dose-response Relationship for Carcinogenicity in the Rat Liver with Low Doses of 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline or N-Nitrosodiethylamine
• P7-44 Toxicity Evaluation of Bt protein with 28-days dietary administration to gastric-acid reduced rat models(GENERAL TOXICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
• P6-43 Screening of chemopreventive agents using a medium-term pancreas carcinogenesis model in hamsters(DRUG METABOLISM/CARCINOGENICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
• Dose-related changes of oxidative stress and cell proliferation in kidneys of male and female F344 rats exposed to potassium bromate
• Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl) nitrosamine in rats after initiation
• Modulatory effects of hepatic, renal or thyroidal impairments on amitrole-induced thyroid carcinogenesis in rats pretreated with DHPN (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
• Inhibiting Effects of Ethinylestradiol on N-ethyl-M-nitrosourea-Initiated Uterine Carcinogenesis in Transgenic Mice Carrying a Human Prototype C-Ha-ras Gene (rasH2 mice) (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th A
• A possible role of oxidative stress in potassium bromate (KBrO_3) carcinogenesis (ACTIVE OXYGEN) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
• Safety evaluetion of Bt protein by dietary administration to a gastro-intestinal impairment rat model (GENERAL TOXICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
• Promoting Effects of Ethinylestradiol but not Atrazine on N-ethyl-N-nitrosourea-induced Uterine Carcinogenesis in ICR Mice
• Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine
• Modifying Effects of 2,6-Dimethylaniline on Nasal Carcinogenesis in RasH2 Mice Initiated with 4-Methylnitrosamino)-1-(3-pyridyl)-1-butanone
• Lack of Modifying Effects of 2,6-Dimethylaniline on Lung Carcinogenesis in Transgenic Mice Carrying Human Prototype c-Ha-ras Gene Initiated with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
• Difference in the Types of Uterine Tumors between Heterozygous p53-deficient and Wild Type CBA Mice Treated with Ethinylestradiol after N-ethyl-N-nitrosourea Initiation
• Modifying effect of atrazine on DMBA-induced mammary carcinogenesis in ovariectomized rats.(GENERAL SESSION BY POSTER PRESENTATION)(CARCINOGENICITY)
• Effects of Antioxidant 1-O-Hexy1-2,3,5-trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi-organ Carcinogenesis Model
• Lung as a new target in rats of 2-amino-3-methylimidazo[4,5-f]quinoline carcinogenesis : Results of a two-stage model initiated with N-bis(2-hydroxypropyl)nitrosamine
• Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
• Inhibiting Effects of Ethinylestradiol on N-ethyl-M-nitrosourea-Initiated Uterine Carcinogenesis in Transgenic Mice Carrying a Human Prototype C-Ha-ras Gene (rasH2 mice) (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th A
• A Preliminary Study of the Effect of Plantago Ovata Forsk on the Development of 7, 12-Dimethylbenz[a]anthracene-initiated Rat Mammary Tumors under the Influence of Hypercholesterolemia
• Establishment of an in vivo Highly Metastatic Rat Hepatocellular Carcinoma Model
• Combined Chemopreventive Effects of Perilla or Corn Oil and Indomethacin in a Rat Medium-Term Multiorgan Carcinogenesis Model
• Modifying Effects of Genistein, 4-Nonylphenol and Methoxychlor on N-ethyl-N-nitrosourea-induced Uterine Carcinogenesis in RasH2 Transgenic Mice Harboring a Human Prototype C-Ha-ras Gene
• The Mouse rasH2/BHT Model as an in vivo Rapid Assay for Lung Carcinogens
• Enhancing Effects β-Estradiol 3-Benzoate but Not Methoxychlor on the Promotion/Progression Stage of Chemically-induced Mammary Carcinogenesis in Ovariectomized Rats
• GONADAL TOXICITY OF AN ETHANOL EXTRACT OF PSORALEA CORYLIFOLIA IN A RAT 90-DAY REPEATED DOSE STUDY
• The Utility of N-nitrosamines as Initiators for a 26-Week Rat Two-Stage Nasal Carcinogenesis Model
• Enhancement by Cigarette Smoke Exposure of 2-Amino-3,8-dimethylimidazo [4,5-f] quinoxaline-induced Rat Hepatocarcinogenesis in Close Association with Elevation of Hepatic CYP1A2
• Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
• Inhibiting Effects of Ethinylestradiol on N-ethyl-M-nitrosourea-Initiated Uterine Carcinogenesis in Transgenic Mice Carrying a Human Prototype C-Ha-ras Gene (rasH2 mice) (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th A
• Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
• Inhibiting Effects of Ethinylestradiol on N-ethyl-M-nitrosourea-Initiated Uterine Carcinogenesis in Transgenic Mice Carrying a Human Prototype C-Ha-ras Gene (rasH2 mice) (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th A
• Inhibiting Effects of Ethinylestradiol on N-ethyl-M-nitrosourea-Initiated Uterine Carcinogenesis in Transgenic Mice Carrying a Human Prototype C-Ha-ras Gene (rasH2 mice) (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th A
• Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
• Development of invasive follicular cell carcinomas in a rat thyroid carcinogenesis model : Biological impact of capsular inflammation and reduced cyclooxygenase-2 expression
• Thesaurus for histopathological findings in publically available reports of repeated-dose oral toxicity studies in rats for 156 chemicals
• Involvement of Lipid Peroxidation in Spontaneous Pancreatitis in WBN/Kob Rats
• Possible enhancing effects of atrazine on growth of 7, 12-dimethylbenz(a) anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats
• Renal Carcinogenicity of Concurrently Administered Fish Meal and Sodium Nitrite in F344 Rats
• TIME COURSE OBSERVATION OF THYROID PROLIFERATIVE LESIONS AND SERUM LEVELS OF RELATED HORMONES IN RATS TREATED WITH KOJIC ACID AFTER DHPN INITIATION
• Inhibition by β-Carotene of Upper Respiratory Tumorigenesis in Hamsters Receiving Diethylnitrosamine Followed by Cigarette Smoke Exposure
• Synergistic Effects of High-dose Soybean Intake with Iodine Deficiency, but Not Sulfadimethoxine or Phenobarbital, on Rat Thyroid Proliferation
• Lack of Effect of Soy Isoflavone On Thyroid Hyperplasia in Rats Receiving an Iodine-deficient Diet
• P-14 Effects of antioxidants on spontaneous hepatic and renal lesions in LEC rats.(Proceedings of the 27th Annual Meeting)
• Lack of Modification by Environmental Estrogenic Compounds of Thyroid Carcinogenesis in Ovariectomized Rats Pretreated with N-bis(2-hydroxynronyl)nitrosamine (DHPN)
• Lack of Modifying Effects of Environmental Estrogenic Compounds on the Development of Thyroid Proliferative Lesions in Male Rats Pretreated with N-Bis(2-hydroxypropyl)nitrosamine(DHPN)
• Inhibitory Effects of 1'-Acetoxychavicol Acetate on N-Nitrosobis(2-oxopropyl)-amine-induced Initiation of Cholangiocarcinogenesis in Syrian Hamsters
• Concurrent Administration of Fish Meal and Sodium Nitrite Does not Promote Glandular Stomach Carcinogenesis in Rats after Treatment with N-methyl-N'-nitro-N-nitrosoguanidine
• Antimutagenic and Anticarcinogenic Properties of Kyo-yasai, Heirloom Vegetables in Kyoto
• 22D-10-1 Effects of Oltipraz on Spontaneous Hepatitis of LEC Rats.
• INFLUENCES OF LONG-TERM ADMINISTRATION OF 24R, 25-DIHYDROXYVITAMIN D_3, A VITAMIN D_3 DERIVATIVE, IN RATS
• Cellular distributions of molecules with altered expression specific to thyroid proliferative lesions developing in a rat thyroid carcinogenesis model
• Pathological assessment of the nervous and male reproductive systems of rat offspring exposed maternally to acrylamide during the gestation and lactation periods-a preliminary study
• Erratum : Thesaurus for histopathological findings in publically available reports of repeated-dose oral toxicity studies in rats for 156 chemicals
• Inhibition of Degranulation of RBL-2H3 Cells by Casein Kinase II Substrate Peptide
• Harman and Norharman Suppressed but NaNO_2 Enhanced the Development of Preneoplastic Liver Cell Foci in 2-Amino-3,8-Dimethylimidazo[4,5-f]Quinoxaline (MeIQx)-Treated Rats
• DOSE-THRESHOLD FOR THYROID TUMOR-PROMOTING EFFECTS OF ORALLY AMINISTERED KOJIC ACID IN RATS AFTER INITIATION WITH N-bis(2-HYDROXYPROPYL) NITROSAMINE
• TOXICITY AND BLOOD CONCENTRATIONS OF XYLAZINE AND ITS METABOLITE, 2, 6-DIMETHYLANILINE, IN RATS AFTER SINGLE OR CONTINUOUS ORAL ADMINISTRATIONS
• 21B-04-1 Preliminary Repeated Dose (28 Days) Oral Toxicity Study of Flutamide to Establish the Efficacy of the "Enhanced OECD Test Guideline 407" in Rats.
• Absence of Tumor Promoting Activity of Xylazine in a Two-stage Nasal Carcinogenesis Model in N-bis(2-hydroxypropyl)nitrosamine-treated Rats
• O-14 Mechanistic studies on testicular toxicity of Psoralea corylifolia extract in rats.(Proceedings of the 27th Annual Meeting)
• Molecular profiling of genes showing altered expression in the livers of rats treated with non-genotoxic hepatocarcinogens for long-term (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
• Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat
• Rhabdomyosarcoma in the Abdominal Cavity of a 12-Month-Old Female Donryu Rat
• Mutagenicity of Combined Treatment with Sodium Nitrite and Ascorbic Acid in Bacterial and Mammalian Cells
• Problems in the risk assessment of carcinogenic chemicals : from the viewpoint of long-term carcinogenicity studies (SYMPOSIUM3: RECENT TOPICS ON THE RISK ASSESSMENT OF CHEMICAL CARCINOGENS) (Proceedings of the 30th Annual Meeting)
• Inhibitory effects of aminoguanidine on thyroid follicular carcinoma development in inflamed capsular regions of rats treated with sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation
• Effects of Clofibrate in the CB6F1-TgHras2 Mice
• Carcinogenic potential of alizarin and rubiadin, components of madder color, in a rat medium-term multi-organ bioassay
• Disappearance of gender-related difference in the toxicity of benzotriazole ultraviolet absorber in juvenile rats
• Gene Expression Profiling and Cellular Distribution of Molecules with Altered Expression in the Hippocampal CA1 Region after Developmental Exposure to Anti-Thyroid Agents in Rats
• Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats
• Female heterozygous (+/fa) Zucker rats as a novel leptin-related mammary carcinogenesis model
• Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat
• Reporter gene mutation in the livers of gpt delta mice treated with 5-(hydroxymethyl)-2-furfural, a contaminant of various foods
• Undifferentiated Sarcoma of the Salivary Gland in a Mongolian Gerbil (Meriones unguiculatus)
• Rhabdomyosarcoma in the Abdominal Cavity of a 12-Month-Old Female Donryu Rat
• Antimutagenic and Anticarcinogenic Properties of Kyo-yasai, Heirloom Vegetables in Kyoto

もっと見る 閉じる

スポンサーリンク