ABSTRACT
SHENMAI injection, a prescription comprised of Panax ginseng and Ophiopogon japonicas, is being extensively applied in the field of cardio-protection and immune-modulation in China. Ginsenosides are the main active components in SHENMAI injection. In order to capture and analyze the pharmacokinetic profile of major ginsenosides of SHENMAI injection in Beagle dogs, liquid chromatography equipped with electro-spray ionization and tandem mass spectrometry method was applied in simultaneous determination for protopanaxatriol type ginsenoside [Re, Rf, Rg1], protopanaxadiol type ginsenoside [Rb2, Rb1, Rd, Rc] and oleanolic acid type ginsenoside [Ro]. A C18 column [150 × 2.1mm, 5micro m] and a linear gradient program were used to achieve chromatographic separation, with 0.02% acetic acid solution and acetonitrile. I.S. and ginsenosides were detected by LC-MS/MS in selective reaction mode. Good linearity spanning 5- 1500ng/mL was achieved with the R[2] values higher than 0.99 for all analytes. Limit of quantification of all analytes were 3ng/mL. Intra- and inter-day precisions ranges from 0.47 to15.68 % and accuracies were within the range of 85.27-117.57%. Validated analyzing method was then used in the pharmacokinetic experiment for SMI in dogs. The results showed that the pharmacokinetic profile of protopanaxadiol, protopanaxatriol and oleanolic acid type ginsenoside were significant difference in dogs. Protopanaxadiol type ginsenosides exhibited an extremely higher level of exposure and a much slower elimination process. Whereas protopanaxatriol type ginsenosides were quickly eliminated. We concluded that 20 [S] - protopanaxadiol type ginseno sides could be a potential pharmacokinetic marker of SHENMAI injection
ABSTRACT
Doxorubicin (Dox) is an effective wide-spectrum antitumor drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. The mechanisms of cardiotoxicity have not been clearly elucidated, but are known to involve oxidative stress, mitochondrial dysfunction and apoptosis. Autophagy is a lysosome-dependent protein degradation pathway. More recently, many studies have suggested that autophagy plays an important role in Dox-induced cardiotoxicity. This paper gives a systematic review of the role of autophagy in Dox-induced cardiotoxicity.
ABSTRACT
Aim: To explore pharmacokinetics of NG-nitro-D-arginine (D-NNA)and NG-nitro-L-arginine (L-NNA)in conscious rats. Methods: The plasma concentration of D-NNA and L-NNA were determined by chiral ligand exchange method with capillary electrochromatography (CEC). Pharmacokinetic parameters were obtained using non-compartment model and were fitted using a computer program DAS. Results: The metabolism of D-NNA and L-NNA exhibited significant isomeric selectivity. The CL and T1/2 of D-NNA and D-NNA were(0.46 ± 0.02) ml·h-1·kg-1 vs (0.17 ± 0.03) ml·h-1·kg-1 (P < 0.05) and (1.44 ± 0.28) h vs (3.48 ± 0.41) h (P < 0.05), respectively. Unidirectional chiral conversion rate of D-NNA to L-NNA was (50.03 ± 8.5)%. Conclusion: The stereoselective pharmacokinetics of N G-nitro-arginine observed maybe due to the unidirectional chiral inversion of D-NNA to L-NNA.