Mitochondria are Main Targets of Time/Dose-Dependent Oxidative Damage-Based Hepatotoxicity Caused by Rhizoma Dioscoreae Bulbiferae in Mice

Background:Rhizoma Dioscoreae bulbiferae could cause liver damage,which limited its application in the clinic.Aims and Objectives:To explore the mechanism of hepatotoxicity of Rhizoma Dioscoreae bulbiferae in mice.Materials and Methods:In the present study,the water extraction of Rhizoma Dioscoreae bulbiferae(W.E.R)was administrated via intragastrical with Low(19.6 g/kg),Middle(28.0 g/kg),and High(40.0 g/kg)dose in mice.At each time point 14 days,21 days,and 28 days,the body weight,liver coefficient,indexes of liver function alkaline phosphatase(ALP),alanine aminotransferase(ALT)and aspartate transaminase(AST),various biochemical biomarkers of liver tissue and mitochondria were detected and analyzed.Results:We found that W.E.R could decrease the body weight,increase the liver coefficient and the expression levels of indexes of liver function in mice.Next,we investigated that W.E.R could increase the expression levels of reactive oxygen species(ROS)and malondialdehyde(MDA),decrease the expression levels of adenosine triphosphate(ATP)and improve the enzyme activities of total superoxide dismutase(SOD).Third,we found that W.E.R could increase the enzyme activities of manganese-superoxide dismutase,decrease the enzyme activities of sodium-potassium adenosine triphosphatase(Na+-K+-ATPase)and calcium-magnesium adenosine triphosphatase(Ca 2+-Mg 2+-ATPase).Finally,we analyzed that there were significant negative correlations between body weight,expression level of ATP,activity of Na+-K+-ATPase,activity of Ca 2+-Mg 2+-ATPase and time,dose.There were significant positive correlations between liver coefficient,ALP,ALT,AST,expression levels of ROS,MDA and time,dose.Conclusion:All the results above indicated that W.E.R could cause the hepatotoxicity based on the oxidative damage in mice,which and mitochondria might be the main targets.

Interspecific Crossing between Yam Species (Dioscorea rotundata and Dioscorea bulbifera) through in Vitro Ovule Culture

In the present study, in vitro ovule culture technique was used to obtain interspecific cross combination of Dioscorea rotundata ufenyi and Dioscorea bulbifera wild. Ten days after pollination, ovules were excised and cultured onto 1/2 strength Murashige and Skoog (MS) medium (Basal salt mixture + Vitamins) supplemented with 6% sucrose, 0.7% agar and plant growth hormones such as GA3, BAP, Picrolam and TDZ. Cultured ovules were transferred on 1/2 MS medium with 3% sucrose and 0.7% agar after three weeks. 40 days after pollination, germination was observed from 7 months cultured ovule between D. rotundata ufenyi x D. bulbifera wild. Hybridity of the regenerated plant was checked by flow cytometric method. A close relation was observed between the fluorescence intensity of the obtained progeny with one of the parents’ fluorescence. The observed progeny can be closely correlated with an apomictic tissue from an ovule parent of D. rotundata ufenyi. Plantlets derived from ovule culture were proliferated through in vitro shoot multiplication with hormonal concentration (0.5 mg/l BAP) supplemented with 1/2 strength MS medium. Obtained ovule culture derived in vitro plantlets were successfully hardened, acclimatized and transferred to the field, where they survived and grew normally. In plant breeding, interspecific crossing is very important technique, enabling the time needed to produce homozygous lines to be shortened as compared to the conventional plant breeding techniques.

The crucial role of metabolic regulation in differential hepatotoxicity induced by furanoids in Dioscorea bulbifera

Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in vitro,but reasonable explanations for the differential hepatotoxicity have not been provided.Herein,the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs(diosbulbins A,B,C,F).In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3 A4 at the atomic level were simulated by molecular docking.Results showed that DLs exhibited varied cytotoxicities,and that CYP3 A4 played a modulatory role in this process.Moreover,structural variation may cause different affinities between DLs and CYP3 A4,which was positively correlated with the observation of cytotoxicity.In addition,analysis of the glutathione(GSH)conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs,whereas,GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity.Collectively,our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.