Effects of Kojic Acid on Thyroidal Functions in Rats by Single-Dose Administration and in Cultured Rat Thyroid Cells (Frtl-5 Cells)

Higa, Yoshitaka; Ohkubo, Atsushi; Kitajima, Shunichi; Moriyasu, Matuko; Kariya, Kimio

doi:10.2131/jts.27.423

Cited by 13 publications

(10 citation statements)

References 12 publications

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“…Evidence indicating formation of DNA adducts in the thyroids of rats given diet containing 2% KA for 2 weeks was lacking (Tamura et al -ing to DNA damage was not induced. As for modifying effects of KA on thyroidal function, inhibition of iodine KA at a massive dose or for a long administration period (Tamura et al, 1999b;Higa et al, 2002). The present and previously reported results thus indicate that carcinogenic effects of KA in the rat thyroid are associated with inhibi--roid, and it can be concluded that thyroid tumors were induced via promoting effects.…”

Section: Discussionsupporting

confidence: 60%

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

et al. 2009

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-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 -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 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 227 mg/kg body weight/day in male rats.

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Section: Discussionsupporting

confidence: 60%

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

et al. 2009

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“…[4][5][6][7] Used as an important material in antibiotic and pesticide productions, 3,8,9) kojic acid has been shown to act as a competitive and reversible inhibitor of animal and plant polyphenol oxidases, xanthine oxidase, and D-and some L-amino acid oxidases. [10][11][12][13][14][15][16] About the toxicological aspect, the acute or subchronic toxicity resulting from an oral dose of kojic acid has never been reported, but convulsions may occur if kojic acid is injected. Continuous administration of high doses of kojic acid in mice resulted in induction of thyroid adenomas in both sexes.…”

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confidence: 99%

Toxicogenomics of Kojic Acid on Gene Expression Profiling of A375 Human Malignant Melanoma Cells

Cheng

Liu

Sheu

et al. 2006

Biological & Pharmaceutical Bulletin

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Kojic acid is a natural product and normally used as a food additive and preservative, a skin-whitening agent in cosmetics, a plant growth regulator and a chemical intermediate. Using DNA microarray technology, the overall biological effects of kojic acid on the gene expression profiling of a human skin A375 malignant melanoma cells were examined. After treatment with kojic acid, a total of 361 differentially expressed genes were distinctively changed with 136 up-regulated genes and 225 down-regulated genes. We used the bioinformatics tool to search the gene ontology and category classification of differentially expressed genes that provided the useful information of expressed genes belonging to cellular component, molecular function and biological process in regulation of melanogenesis. Seven down-regulated genes of APOBEC1, ARHGEF16, CD22, FGFR3, GALNT1, UNC5C and ZNF146 that were typically validated by the real-time quantitative PCR (RT-qPCR) analysis technology showed to be the tumor suppressor genes in melanoma cancer cells. Thus, microarray technology coupled with RT-qPCR offered a high throughput method to explore the number of differentially expressed genes responding to kojic acid and their biological functions, and led to more understanding of kojic acid effects on skin cancer therapy and related side effects. Moreover, the differentially expressed genes may become useful markers of skin malignant melanoma for further diagnostic and therapeutic applications.

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“…There are some well-known melanin synthesis inhibitors, including kojic acid, arbutin, PTU or hydroquinone, which are being utilized globally as cosmetics ingredients at present. However, these melanogenic inhibitors may induce human skin tumorigenicity at high concentration doses or frequent use (26)(27)(28). There are concentration standards for every country to use kojic acid, arbutin or other chemical ingredients as a composition in cosmetic additives.…”

Section: Discussionmentioning

confidence: 99%

Identifying melanogenesis inhibitors from Cinnamomum subavenium with in vitro and in vivo screening systems by targeting the human tyrosinase

Wang¹,

Chen²,

Wen³

2010

Experimental Dermatology

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are equal contributions to this paper.Abstract: Tyrosinase is known to be the first two and rate-limiting enzyme in the synthesis of melanin pigments responsible for colouring skin, hair and eyes. Tyrosinase inhibition is one major strategy used to treat hyperpigmentation. In human skin melanocytes, the cellular tyrosinase inhibition was examined by the conversion of L-tyrosine and oxidation of L-DOPA to dopaquinone. We evaluated the skin pigmentation inhibitor effects with both in vitro and in vivo systems to find skinwhitening agents without cytotoxic concerns. First, linderanolide B and subamolide A were isolated from the stems of Cinnamomum subavenium and exhibited mushroom tyrosinase inhibition. Then, these two herbal compounds were proved to have good pigmentation inhibitory abilities at low doses and demonstrated free cytotoxicities to normal human skin cells and zebrafish system. With molecular docking, in a virtual model of human tyrosinase, linderanolide B and subamolide A displayed meta lcoordinating interactions with Cu 2+ ions. The results obtained from biological assays showed that linderanolide B and subamolide A possessed anti-tyrosinase properties, which exhibited potential for application in medical cosmetology.

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Effects of Kojic Acid on Thyroidal Functions in Rats by Single-Dose Administration and in Cultured Rat Thyroid Cells (Frtl-5 Cells)

Cited by 13 publications

References 12 publications

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

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

Toxicogenomics of Kojic Acid on Gene Expression Profiling of A375 Human Malignant Melanoma Cells

Identifying melanogenesis inhibitors from Cinnamomum subavenium with in vitro and in vivo screening systems by targeting the human tyrosinase

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