Interaction Effects between Doxorubicin and Hernandezine on the Pharmacokinetics by Liquid Chromatography Coupled with Mass Spectrometry.

Doxorubicin (DOX) is an effective anti-tumor drug widely used in clinics. Hernandezine (HER), isolated from a Chinese medicinal herb, has a selective inhibitory effect on DOX multidrug resistance, making DOX more effective in treating cancer. The aim of this study was to investigate the effect of the interaction of HER and DOX on pharmacokinetics. Male Sparague-Dawley rats were randomly divided into three groups: a single DOX group, a single HER group, and a combination group. Plasma concentrations of DOX and HER were determined by the LC-MS/MS method at specified time points after administration, and the main pharmacokinetic parameters were estimated. The results showed that there were significant differences in the Cmax and AUC0-∞ of DOX in the single drug group and combined drug group, indicating that HER could improve the absorption of DOX. However, DOX in combination, in turn, reduced the free drug concentration of HER, possibly because DOX enhanced the HER drug-protein binding effect. The results could be used as clinical guidance for DOX and HER to avoid adverse reactions.

Saikosaponin-D attenuates heat stress-induced oxidative damage in LLC-PK1 cells by increasing the expression of anti-oxidant enzymes and HSP72.

Heat stress stimulates the production of reactive oxygen species (ROS), which cause oxidative damage in the kidney. This study clarifies the mechanism by which saikosaponin-d (SSd), which is extracted from the roots of Bupleurum falcatum L, protects heat-stressed pig kidney proximal tubular (LLC-PK1) cells against oxidative damage. SSd alone is not cytotoxic at concentrations of 1 or 3 µg/mL as demonstrated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To assess the effects of SSd on heat stress-induced cellular damage, LLC-PK1 cells were pretreated with various concentrations of SSd, heat stressed at 42°C for 1 h, and then returned to 37°C for 9 h. DNA ladder and MTT assays demonstrated that SSd helped to prevent heat stress-induced cellular damage when compared to untreated cells. Additionally, pretreatment with SSd increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) but decreased the concentration of malondialdehyde (MDA) in a dose-dependent manner when compared to controls. Furthermore, real-time PCR and Western blot analysis demonstrated that SSd significantly increased the expression of copper and zinc superoxide dismutase (SOD-1), CAT, GPx-1 and heat shock protein 72 (HSP72) at both the mRNA and protein levels. In conclusion, these results are the first to demonstrate that SSd ameliorates heat stress-induced oxidative damage by modulating the activity of anti-oxidant enzymes and HSP72 in LLC-PK1 cells.