目的;利用斑马鱼模型研究中药乳香的发育毒性作用及可能的毒性靶器官。方法:使用甲醇提取获得的乳香提取物(0.48、0.96、1.59、2.39、4.78μg/mL)处理4hpf(hours post fertilization)AB系斑马鱼胚胎4d,观察斑马鱼胚胎24、48、72、96hpf...目的;利用斑马鱼模型研究中药乳香的发育毒性作用及可能的毒性靶器官。方法:使用甲醇提取获得的乳香提取物(0.48、0.96、1.59、2.39、4.78μg/mL)处理4hpf(hours post fertilization)AB系斑马鱼胚胎4d,观察斑马鱼胚胎24、48、72、96hpf的死亡率、48hpf和72hpf的孵化率、96hpf的畸形率和体长。进一步利用同样浓度乳香提取物处理4hpf心肌转基因标记品系Tg(cmlc2:EGFP)斑马鱼胚胎3d,观察72hpf时斑马鱼胚胎的心率、心包面积、静脉窦和动脉球(SV-BA)距离,评价乳香对斑马鱼胚胎的心脏发育毒性。采用吖啶橙染色法初步考查乳香造成心脏毒性的作用机制。结果:48hpf 1.59、2.39、4.78μg/mL乳香可引起斑马鱼孵化延迟(P<0.01),48hpf 4.78μg/mL乳香致斑马鱼发育畸形(P<0.01),96hpf 2.39、4.78μg/mL乳香致斑马鱼体长缩短(P<0.05,P<0.01),具体会引起心脏、鱼鳔、卵黄囊等器官组织的发育畸形;2.39、4.78μg/mL乳香可造成斑马鱼胚胎心脏心率降低、心包水肿、SV-BA距离增加(P<0.01),心脏毒性可能与心肌细胞凋亡有关。结论:乳香对斑马鱼胚胎发育具有一定毒性作用,心脏、鱼鳔、卵黄囊为可能的毒性靶器官/组织,其心脏毒性可能与其诱导心肌细胞发生凋亡有关。展开更多
Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical applicatio...Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.展开更多
Chemotherapy induced cardio-toxicity is a well known side effect of anticancer treatments, moreover the 70% of all tumors involve patients over 65 years-old, frequently with cardiac co- morbidity. We evaluated the fea...Chemotherapy induced cardio-toxicity is a well known side effect of anticancer treatments, moreover the 70% of all tumors involve patients over 65 years-old, frequently with cardiac co- morbidity. We evaluated the feasibility of the application during chemotherapy administration of some of the most recent diagnostic techniques as 12-diagnostic leads telemetry, 7 days EKG monitoring device (R-Test Evolution 3R), blood level dosage of Brain Natriuretic Peptide (BNP) and Ischemia Modified Albumin (IMA). Some sub-clinical changes in the investigated parameters were found in patients undergoing chemotherapy, mostly containing fluorouracil, as shown in the following paper. Far from suggesting a widespread use of these methods during chemotherapy administration, we think that some more tools are needed to prevent cardiac toxicity in high-risk patients and some of what we studied may deserve further valuation in chemotherapy clinical trials.展开更多
基金Acknowledgments This work was supported by the National Basic Research Program of China （2012CB934004）, the National Funds for Distinguished Young Scientists （31325010）, the Key Research Program of the Chinese Academy of Sciences （KGZD-EW-T06） and the National Natural Science Foundation of China （31300822）.
文摘Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.
文摘Chemotherapy induced cardio-toxicity is a well known side effect of anticancer treatments, moreover the 70% of all tumors involve patients over 65 years-old, frequently with cardiac co- morbidity. We evaluated the feasibility of the application during chemotherapy administration of some of the most recent diagnostic techniques as 12-diagnostic leads telemetry, 7 days EKG monitoring device (R-Test Evolution 3R), blood level dosage of Brain Natriuretic Peptide (BNP) and Ischemia Modified Albumin (IMA). Some sub-clinical changes in the investigated parameters were found in patients undergoing chemotherapy, mostly containing fluorouracil, as shown in the following paper. Far from suggesting a widespread use of these methods during chemotherapy administration, we think that some more tools are needed to prevent cardiac toxicity in high-risk patients and some of what we studied may deserve further valuation in chemotherapy clinical trials.
