OBJECTIVE: To study the pathological change and the toxic mechanism of Dioscorea bulbifera L in mice. METHODS: Sixty ICR mice were randomly assigned to four groups poisoned respectively with 200% Dioscorea bulbifera L of 1/4 LD50, 1/10LD50, 1/30LD50 and a control group treated with distilled water by oral administration. All animals were pathologically examined with LM and some of them were examined with TEM when the mice died during the experiment or the survival mice were sacrificed after thirty days. RESULTS: The pathological changes showed fatty change and the increasing glycogen of liver cells; degeneration and necrosis of the epithelia of uriniferous tubules. The serum BUN and ALT of the experimental groups mice were higher than that of control group. Enzyme histochemical staining showed the decreasing activity of G-6-P and SDH in the liver cells in the experimental groups. CONCLUSION The experiment suggests that the target organs were liver and kidney. The toxic mechanism of Dioscorea bublifera L was the damage of the mitochondrional and endoplasmic reticulum membrane directly. As a result, the activity of the SDH and G-6-P decreased, the metabolism was affected.
Animals ; Chemical and Drug Induced Liver Injury/pathology* ; Dioscorea/toxicity* ; Endoplasmic Reticulum/pathology* ; Female ; Forensic Medicine ; Kidney/pathology* ; Male ; Mice ; Mice, Inbred ICR ; Mitochondria, Liver/pathology* ; Random Allocation

Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.
Animals ; Bile Acids and Salts ; metabolism ; Chemical and Drug Induced Liver Injury ; metabolism ; Cholic Acid ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dioscorea ; toxicity ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Heterocyclic Compounds, 4 or More Rings ; isolation & purification ; toxicity ; Least-Squares Analysis ; Male ; Mice ; Mice, Inbred ICR ; Plants, Medicinal ; toxicity ; Principal Component Analysis ; Rhizome ; toxicity ; Tandem Mass Spectrometry ; methods ; Taurochenodeoxycholic Acid ; metabolism ; Taurocholic Acid ; metabolism ; Taurodeoxycholic Acid ; metabolism

OBJECTIVETo explore the liver-toxic fraction in Rhigoma of Dioscorea bulbifera.

METHODThe rats were randomized into four groups: control group (20% PVP-water), T001(10% total methanol extraction), F002(5% chloroform fraction) and F003(5% methanol fraction). Direct bilirubin (DBil) and Glutamic-pyruvic transaminase (GPT) were examined, and liver index was measured. The histological and morphological observations were performed with optical and electrical microscope.

RESULTT001 and F002 showed significant liver toxicity.

CONCLUSIONThe chloroform fraction was the liver-toxic fraction of D. bulbifera.

Alanine Transaminase ; blood ; Animals ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; pathology ; Dioscorea ; chemistry ; Drugs, Chinese Herbal ; toxicity ; Female ; Liver ; pathology ; ultrastructure ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The present study was designed to observe the protection of Grateloupia filicina polysaccharide (GFP) against hepatotoxicity induced by Dioscorea bulbifera L in mice and its underlying mechanism. GFP was intragastrically (ig) given to mice at various doses. After 6 days, the mice were treated with ethyl acetate extract of Dioscorea bulbifera L (EF, ig). Serum levels of alanine/aspartate aminotransferase (ALT/AST), alkaline phosphatase (ALP), total bilirubin (TB) were measured, and liver histological evaluation was conducted. Furthermore, reductions of liver glutathione (GSH) amount and glutamate cysteine ligase (GCL) activity were tested. The expressions of GCL-c, GCL-m, and HO-1 (heme oxygenase-1) in liver were observed by Western-blot. The results showed that GFP (600 mg x kg(-1)) decreased EF-induced the increase of serum ALT, AST and TB, and GFP (400, 600 mg x kg(-1)) inhibited EF-induced the increase of serum ALP. Liver histological evaluation showed that the liver injury induced by EF was relieved after treated with GFP. GFP further increased liver GSH amount and reversed EF-induced the decrease of GCL activity. The Western-blot result showed that GFP augmented EF-induced the increase of HO-1, and reversed EF-induced the decrease of GCL-c. In conclusion, GFP can act against the oxidative stress liver injury induced by Dioscorea bulbifera L in mice.
Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; blood ; metabolism ; Dioscorea ; toxicity ; Glutamate-Cysteine Ligase ; metabolism ; Glutathione ; metabolism ; Heme Oxygenase-1 ; metabolism ; Heterocyclic Compounds, 4 or More Rings ; antagonists & inhibitors ; isolation & purification ; toxicity ; Liver ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Oxidative Stress ; drug effects ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Random Allocation ; Rhodophyta ; chemistry