Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels. Following liquid chromatography-tandem mass analysis of the DIOB content of DB extract, male ICR mice were randomly orally administered DB or DIOB for 14 days. Liver injury was assessed by histopathological and biochemical analysis of liver fuction. The levels of transporter protein and mRNA were determined by western blotting and real-time PCR. Liver function and histopathological analysis indicated that both DB and DIOB could induce liver injury in mice, and that DIOB might be the primary toxic compound in DB. Moreover, down-regulation of Mrp2 blocked the excretion of bilirubin, glutathione disulfide, and bile acids, leading to the accumulation of toxic substrates in the liver and a redox imbalance. We identified down-regulated expression of Mrp2 as potential factors linked to increased serum bilirubin levels and decreased levels of glutathione in the liver and increased liver injury severity. In summary, our study indicates that down-regulation of Mrp2 represents the primary mechanism of DB- and DIOB-induced hepatotoxicity, and provides insight into novel therapies that could be used to prevent DB- and DIOB-mediated liver injury. 相似文献
This study sought to identify variation by gender in the associations between religious service attendance from adolescence to young adulthood and seven measures of lifetime and short-term substance use.
Methods
To conduct this nationally representative study, data from the Add Health Surveys was abstracted from Waves I and IV (N = 3,223) to construct four types of service attendance (non-attenders, attenders only as adolescents, attenders only in young adulthood, and consistent attenders). A series of logistic regressions were conducted to identify the independent effects of each pattern of service attendance on each substance among all black young adults, as well as male and female sub-samples.
Results
Analysis revealed consistent attenders were generally less likely to use substances, with the effects being strongest among females. Among young adult only attenders, males recorded lower odds across all three short-term measures whereas females reported lower odds only for monthly cigarette use.
Conclusion
The protective effects of religious service attendance are more robust for African Americans who consistently attend in adolescence and young adulthood, especially among females.
