β-Cyclodextrin: 52-Week toxicity studies in the rat and dog

Bellringer, M.E.; Smith, Traci; Read, Raymond C.; Gopinath, C.; Olivier, Ph.

doi:10.1016/0278-6915(94)00149-i

Cited by 75 publications

(39 citation statements)

References 5 publications

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“…Rather, a higher dose of b-cyclodextrin increased AST and ALT. 32 Our maximum dose of b-cyclodextrin was 0.5%. For this reason, b-cyclodextrin in our experiment was not high enough to affect AST and ALT levels.…”

Section: Discussionmentioning

confidence: 99%

Crepidiastrum denticulatumExtract Protects the Liver Against Chronic Alcohol-Induced Damage and Fat Accumulation in Rats

Yoo

Kang

Yun

et al. 2014

Journal of Medicinal Food

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Alcohol is a severe hepatotoxicant that causes liver abnormalities such as steatosis, cirrhosis, and hepatocarcinoma. Crepidiastrum denticulatum (CD) is a well-known, traditionally consumed vegetable in Korea, which was recently reported to have bioactive compounds with detoxification and antioxidant properties. In this study, we report the hepatoprotective effect of CD extract against chronic alcohol-induced liver damage in vivo. The rats that were given CD extract exhibited decreased alanine aminotransferase, aspartate aminotransferase, and c-glutamyl transpeptidase activities, which are liver damage markers that are typically elevated by alcohol consumption. The results were confirmed by histopathology with hematoxylin and eosin staining. Chronic alcohol consumption induced the formation of alcoholic fatty liver. However, treatment with CD extract dramatically decreased the hepatic lipid droplets. Treatment with CD extract also restored the antioxidative capacity and lipid peroxidation of the liver that had been changed by alcohol consumption. Furthermore, treatment with CD extract normalized the activities of the antioxidative enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase, which had been decreased by alcohol consumption. The results indicate that CD extract has protective effects against chronic alcohol hepatotoxicity in rats by increasing the liver's antioxidant capacity, and has potential as a dietary supplement intervention for patients with alcohol-induced liver damage.

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Section: Discussionmentioning

confidence: 99%

Crepidiastrum denticulatumExtract Protects the Liver Against Chronic Alcohol-Induced Damage and Fat Accumulation in Rats

Yoo

Kang

Yun

et al. 2014

Journal of Medicinal Food

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“…These effects are observed not only with HP-β-CD (Gould and Scott, 2005) and SBE-β-CD but also with α-CD (JECFA, 2001;Bar 2004a, 2004b), β-CD (Bellringer et al, 1995), and γ-CD (Lina and Bar 1998;Til and Bar 1998). The parent CDs all are accepted as food additives and "generally recognized as safe" (GRAS).…”

Section: Toxicological Studies Effects On Gastrointestinal Tractmentioning

confidence: 99%

Cyclodextrins

Stella

He²

2008

Toxicol Pathol

628

415

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β-cyclodextrin (β-CD) and other cyclodextrins (CDs) have utility for solubilizing and stabilizing drugs; however, some are nephrotoxic when administered parenterally. A number of workers have attempted to identify, prepare, and evaluate various CD derivatives with superior inclusion complexation and maximal in vivo safety for various biomedical uses. A systematic study led to SBE-β-CD (Captisol), a polyanionic variably substituted sulfobutyl ether of β-CD, as a non-nephrotoxic derivative and HP-β-CD, a modified CD developed by Janssen. SBE-β-CD and HP-β-CD have undergone extensive safety studies and are currently used in six products approved by the Food and Drug Administration (four for Captisol and two for HP-β-CD). They are also in use in numerous clinical and preclinical studies. This article will focus on the issues that led to the development of these two CDs, their safety, characterization, and applications, and especially their ability to improve drug delivery. SBE-β-CD interacts very well with neutral drugs to facilitate solubility and chemical stability, and because of its polyanionic nature, it interacts particularly well with cationic drugs. Complexes between SBE-β-CD and HP-β-CD and various drugs have been shown to rapidly dissociate after parenteral drug administration, to have no tissue-irritating effects after intramuscular dosing, and to result in superior oral bioavailability of poorly water-soluble drugs. The pharmacokinetics, tissue distribution, and cellular effects of some representative CDs, including SBE-β-CD and HP-β-CD, are reviewed. The safety profiles of CDs are discussed, with emphasis on the biological effects of some CDs on the gastrointestinal tract, kidney, and reproduction and development and the carcinogenic potential of CDs. In addition, human experience with CD derivatives, specifically SBE-β-CD and HP-β-CD, indicates that these two CDs are well tolerated in humans and have no adverse effects on the kidneys or other organs following either oral or intravenous administration.

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“…The toxicolooical effects appeared to be related to the structure of the CD. Non-substituted CDs were found to be highly toxic for the kidneys (Brexster et al 1990: Bellringer et al 1995. whereas the toxicitv of substituted CDs varies with the degree and the nature of the substitution (Frijlink et al 1990.…”

mentioning

confidence: 99%

Antiproliferative effect of methyl-β-cyclodextrin in vitro and in human tumour xenografted athymic nude mice

Grosse

Bressolle²,

Pinguet³

1998

Br J Cancer

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Summary The anti-tumour actvity of methyl-p-cyckxdextrin (MEBCD), a cydic oligosaccharide known for its interaction with the plasma membrane, was investigated in vitro and in vivo and compared with that of doxorubicin (DOX) in the human tumour models MCF7 breast carcinoma and A2780 ovanan carcinoma. In vitro proliferation was assessed using the MTT assay. In vivo studies were carmied out using xenografted Swiss nude mice injected weeldy i.p. with MEBCD at 300 or 800 mg kg-, or DOX at 2 mg kg-', durng 2 months. Undrer these conditions, MEBCD was active against MCF7 and A2780 cell lines and tumour xenografts. For each tumour model, the tumoral volume of the xenografted mice treated with MEBCD was at least twofold reduced compared wit the control group. In the MCF7 model, MEBCD (800 mg kg-') was more active than DOX (2 mg kg-1). After 56 days of treatnent with MEBCD, no toxicologically meaningful differences were observed in macroscopic and microscopic parameters compared with controls. The accumulation of MEBCD in normal and tumour tssues was also assessed using a chromatographic method. Results indicated that after a single injection of MEBCD, tumour, liver and kidneys accumulated the highest concentrations of MEBCD. These results provided a basis for the potental therapeutic application of MEBCD in cancer therapy.

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β-Cyclodextrin: 52-Week toxicity studies in the rat and dog

Cited by 75 publications

References 5 publications

Crepidiastrum denticulatumExtract Protects the Liver Against Chronic Alcohol-Induced Damage and Fat Accumulation in Rats

Crepidiastrum denticulatumExtract Protects the Liver Against Chronic Alcohol-Induced Damage and Fat Accumulation in Rats

Cyclodextrins

Antiproliferative effect of methyl-β-cyclodextrin in vitro and in human tumour xenografted athymic nude mice

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