ABSTRACT
This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts (CFs) and its potential mechanism, as well as whether sodium tanshinone IIA sulfonate (STS) has protective effect on CFs and its possible mechanism. Our data demonstrated that X-rays inhibited cell growth and increased oxidative stress in CFs, and STS mitigated X-ray-induced injury. Enzyme-linked immuno-sorbent assay showed that X-rays increased the levels of secreted angiotensin II (Ang II) and brain natriuretic peptide (BNP). STS inhibited the X-ray-induced increases in Ang II and BNP release. Apoptosis and cell cycle of CFs were analyzed using flow cytometry. X-rays induced apoptosis in CFs, whereas STS inhibited apoptosis in CFs after X-ray irradiation. X-rays induced S-phase cell cycle arrest in CFs, which could be reversed by STS. X-rays increased the expression of phosphorylated-P38/P38, cleaved caspase-3 and caspase-3 as well as decreased the expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK 1/2)/ERK 1/2 and B cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (BAX) in CFs, as shown by Western blotting. STS mitigated the X-ray radiation-induced expression changes of these proteins. In conclusion, our results demonstrated that STS may potentially be developed as a medical countermeasure to mitigate radiation-induced cardiac damage.
ABSTRACT
This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bilirubin , Blood , Coronary Disease , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacokinetics , Metabolic Clearance Rate , Models, Biological , Phenanthrenes , Blood , PharmacokineticsABSTRACT
Objective To explore the preparation technology of celastrol/sodium tanshinone IIA sulfonate-coloaded liposome (Cel/STS-CL) and verify the synergistic anti-breast cancer effects in vitro. Methods The optimal ratio of celastrol to sodium tanshinone IIA sulfonate for synergistic anti-breast cancer effect was explored by MTT assay. The liposome was prepared by conventional film dispersion method. The physiochemical properties and morphology were measured by dynamic light scattering (DLS), HPLC, and transmission electron microscopy (TEM), respectively. Meanwhile, the in vitro synergistic anti-breast cancer effect of liposome was investigated by cellular uptake, antiproliferative assay, and cell apoptosis induction using MCF-7 cells as model. Results Hydrophilic sodium tanshinone IIA sulfonate and hydrophobic celastrol were simultaneously encapsulated into liposomes by film dispersion method. The liposome had a nearly spherical shape with a clear bilayer, as well exhibited the particle sizes of (104.7 ± 2.1) nm, narrow polydispersion index (PDI) of (0.217 ± 0.002), and zeta potential of (-48.8 ± 2.3) mV. The encapsulation efficiency of celastrol and tanshinone IIA sulfonate were (82.2 ± 2.7)% and (66.2 ± 2.3)%, respectively. In cellular studies, the cellular uptake of liposome was 30 times higher than that of control group; The half proliferation inhibitory concentration (IC50) was (1.42 ± 0.12) μmol/L against MCF-7 cells with a combined index as 0.81. Besides, 80% of MCF-7 cells were induced to apoptosis by Cel/STS-CL, which was 0.1 time higher than Cel-Lip. Conclusion The preparation of Cel/STS-CL was feasible and efficiently, and promising for the in vitro synergistic anti-breast cancer effect, as well in the further studies.
ABSTRACT
Objective To evaluate the clinical efficacy of sodium tanshinone IIA sulfonate(STS)in the treatment of ad-vanced schistosomiasis. Methods Fifty cases with advanced schistosomiasis admitted to the Touzao Township Hospital of Dong-tai City during the period from November 2012 to November 2013 were treated with STS for 10 days,and the internal diameter of the portal vein,levels of ALT,AST,γ-GT,PIIIP,CIV,HA and LN were measured and compared before and after the adminis-tration of STS. Results The mean levels of all serological parameters except HA were within the normal range before STS treat-ment,while the highest positive rate was detected inγ-GT(26.0%)and HA(54.0%). Following the STS treatment,the mean lev-els of all parameters and the positive rates reduced,with the greatest reduction observed inγ-GT(36.7%)and HA(37.8%);how-ever,the mean HA level was still higher than the normal range. The mean internal diameter of the portal vein reduced from(10.5± 1.7)mm before the STS treatment to(9.8±1.3)mm after the STS administration,with a significant diffrtence(P<0.05). Conclu-sion STS appears effective in the treatment of advanced schistosomiasis.