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Study On The Acute Toxicity, The Distribution In Tissues And The Effect Of The Content Of Serum Ions Elements After Oral Administration Of Glycyrrhetinic Acid

Posted on:2013-11-06Degree:MasterType:Thesis
Country:ChinaCandidate:S CaoFull Text:PDF
GTID:2234330374472685Subject:Pharmacognosy
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Glycyrrhetinic acid as a product of the metabolism of drugs Glycyrrhizic acid through the body. It is the true medicinal ingredients of drugs Glycyrrhizic acid. Glycyrrhizic acid can express widely steroid hormones clinical effect, because of the chemical structure of glycyrrhetinic acid similar than steroid hormones compare with Glycyrrhizic acid. In recent years, studies on Glycyrrhetinic acid pharmacology experiment such as anti-arrhythmic, anti-inflammatory and immune resistance, analgesic, anti-tumor, improving the inner ear hearing capabilities, anti-HIV effect. So the drug of Glycyrrhetinic acid has the clinical prospects for application of food additives, pharmaceuticals, cosmetics and other industries effect. Though the experimental study of Pharmacology will be extended, glycyrrhetinic acid still is not used to the most ingredient drugs on sale. Mainly due to glycyrrhetinic acid on the clinical side effects and toxicity limited its widespread clinical application. This paper uses the following three-part study on clinical application and toxicity effects of glycyrrhetinic acid.One, study on mice’s acute toxicity of oral glycyrrhetinic acidTo study the oral administration of glycyrrhetinic acid on acute toxicity in mice with improvement of Kou’s method of glycyrrhetinic acid, and Excel software to help calculate half to death, the LD50of oral glycyrrhetinic acid is553.09mg/kg, confidence limit95%is468.08~653.54mg/kg. Based on acute toxicity rating criteria recommended by the World Health Organization LD50>500mg/kg as low toxicity level, so glycyrrhetic acid for low-toxicity of drugs. Recorded following administration groups of body weight in mice, the results suggest that dose of980mg/kg following administration of a significant downward trend (P<0.01). Other groups rising weight of mice after7d are smooth and no significant difference compared to normal.Second, the determination of plasma concentration and distribution in tissue after oral administrationIn this study, determination of the glycyrrhetinic acid concentration in five tissues which including heart, liver, spleen, lung and kidney in mices after oral administration of glycyrrhetinic acid60,120,180min, and the glycyrrhetinic acid content in plasma of rats with the change of time. The concentrations of glycyrrhetinic acid in five tissues of the mices at60,80,120min and plamsa of rats were determined by LC-MS/MS method, after oral administration of a single glycyrrhetinic acid. The results express that oral doses of500mg/kg of glycyrrhetinic acid plasma concentration reached the maximum of30753ng/mL after oral administration2h, and the second absorption phenomena be found after24h. Analysis of the concentration of oral glycyrrhetinic acid in five tissues (heart, liver, spleen, lung and kidney)at60,80.120min, and the maximum of glycyrrhetinic acid is3910ng/mL,4399ng/mL,2251ng/mL in liver.The concentrations of glycyrrhetinic acid in all the tissues decline rapidly, and the degree of reduce by heart> lung> spleen> liver, at180min after oral administration. The concentrations of heart, liver, spleen exhibit a significant downward trend (P<0.05) compare with120min after oral administration.Three, the determination of serum elements after oral administrationIn this study, the contents of six elements of Na, K, Ca, Mg, Fe and Cu were determined in serum by flame atomic absorption spectrometry at the conditions of different time periods and administration dosages. The test results showed that in rats after oral administration of glycyrrhetinic acid in serum Na and Cu concentrations of elements and the same trend of glycyrrhetinic acid plasma concentration. Glycyrrhetinic acid in plasma after administration for2h reached the highest level. Meanwhile, the contents of Na and Cu at the administration of glycyrrhetinic acid for4h exhibited a significant increase (P<0.05). With the increase of dose, Na, Cu element concentration increased when the dose of400mg/kg and200mg/kg. The content of Na, Cu compared with control group revealed a significant increase (P<0.05), but the concentration of other elements did not exhibit significant impact.
Keywords/Search Tags:Glycyrrhetic acid, acute toxicity, distribution in vivo, ions element
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