Acute toxicity and sub-chronic toxicity of steroidal saponins from Dioscorea zingiberensis C.H.Wright in rodents |
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Authors: | Yuan Qin Xiaohua Wu Wen Huang Guohua GongDan Li Yang HeYinlan Zhao |
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Affiliation: | Institute for Nanobiomedical Technology and Membrane Biology, State Key Lab of Biotherapy of Human Diseases, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan 4 Road No. 1, Gaopeng Avenue, Gaoxin District, Chengdu 610041, China |
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Abstract: | Ethnopharmacological relevanceSteroidal saponins from Dioscorea zingiberensis are widely used in China for curing cardiovascular diseases. However, there was little toxicological information available on them.Aim of the studyThe study evaluated potential toxicity of the steroidal saponins and analyzed the metabolites in rats.Materials and methodsFor the acute study, the steroidal saponins were administered to kunming mice in single doses of 112.5–9000 mg/kg given by gavage. General behavior adverse effects, mortality and liver histopathological changes were examined. For the sub-chronic toxicity study, Sprague–Dawley rats were gavaged at doses of 127.5, 255 and 510 mg/kg/day for 30 days, then examined the biochemical and hematological parameters. Metabolites in serum were analyzed by HPLC–MS.ResultsThe steroidal saponins caused dose-dependent general behavior adverse effects, mortality and liver histopathological changes in the acute toxicity study. In the sub-chronic toxicity study, 510 mg/kg/day of steroidal saponins increased total bilirubin (TBIL) in serum and decreased protein content in liver significantly. The metabolic process of TBIL in liver includes TBIL intaking, conjugated bilirubin forming, conjugated bilirubin excreting to biliary passage. Treatment with high dose of the steroidal saponins in vivo may lead to vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis. In all doses used in the experiment, the steroidal saponins decreased aspartate aminotransferase (GOT), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) in serum and increased reduced glutathione hormone (GSH), glutathione reductase (GR) and glutathione S-transferases (GST) in liver. Diosgenin was the main metabolite in serum.ConclusionsThe steroidal saponins did not show any sign of toxicity up to oral dose of 562.5 mg/kg in mice. No significant changes of biochemical and hematological parameters in rats (except at 510 mg/kg/day), it was concluded that the steroidal saponins did not appear to have significant toxicity in their traditional uses. |
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Keywords: | GOT, aspartate aminotransferase ALT, alanine aminotransferase AKP, alkaline phosphatase TBIL, total bilirubin GSH, reduced glutathione hormone GR, glutathione reductase GST, glutathione S-transferases GSSG, glutathione disulfide NOAEL, no-observed adverse effect value LOAEL, lowest-observed adverse effect value DX, Di-ao-xin-xue-kang |
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