Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats
Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats
复制标题
氟哌啶醇脂质核心聚合物纳米胶囊减少大鼠血液中的 DNA 损伤以及肝脏和肾脏的氧化应激
DOI：
10.1007/s11051-015-2979-4
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发表时间：
2015
影响因子：
2.5
通讯作者：
M. Burger
中科院分区：
文献类型：
--
作者：
Katiane Roversi;D. Benvegnú;K. Roversi;F. Trevizol;L. T. Vey;F. Elias;R. Fracasso;M. Motta;R. F. Ribeiro;Bruna S. Hausen;R. Moresco;S. Garcia;Cristiane B. Silva;M. Burger
氟哌啶醇（HP）纳米胶囊化提高了治疗效果，延长了药物作用时间，并减少了其运动副作用。然而，鉴于HP在肝脏和肾脏等器官中的毒性，以及缺乏关于聚合物纳米胶囊毒性的知识，我们的目的是验证HP纳米制剂对大鼠肝脏和肾脏中毒性和氧化应激标志物的影响，同时观察血液中引起的损伤。为此，将28只成年雄性Wistar大鼠指定为四个实验组（n = 7），并用载体（C组）、游离氟哌啶醇混悬液（FH组）、空白纳米胶囊混悬液（B-Nc组）和氟哌啶醇负载的脂质核纳米胶囊混悬液（H-Nc组）处理。纳米胶囊制剂呈现约250 nm的尺寸。将所有混悬液给予动物（0.5 mg/kg/天-i. p.）为期28天。我们的研究结果表明，FH引起肝脏损伤，表现为脂质过氧化作用增加，血浆天冬氨酸转氨酶和丙氨酸转氨酶水平升高，以及细胞完整性和维生素C水平降低。在肾脏中，FH治疗引起的损伤程度较轻，通过δ-氨基乙酰丙酸酯酶（ALA-D）活性和VIT C水平降低观察到。此外，FH治疗还与血液中较高的DNA损伤指数有关。另一方面，用H-Nc和B-Nc处理的动物没有显示肝、肾和DNA的损伤。我们的研究表明，氟哌啶醇的纳米胶囊化能够预防通常在肝脏、肾脏和DNA中观察到的亚慢性毒性，因此反映了相对于游离药物的药理学优势。
Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.
DOI：
10.1159/000459097
发表时间：
1982-01-01
期刊：
ENZYME
影响因子：
--
作者：
SASSA, S
通讯作者：
SASSA, S
氟哌啶醇衍生的吡啶鎓代谢物的 MPP() 样神经毒性：体内微透析和体外线粒体研究。
DOI：
--
发表时间：
1994
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Rollema,H;Skolnik,M;D'Engelbronner,J;Igarashi,K;Usuki,E;CastagnoliJr,N
通讯作者：
CastagnoliJr,N
人肝微粒体将氟哌啶醇及其四氢吡啶脱水产物转化为潜在神经毒性吡啶代谢物的研究。
DOI：
10.1021/tx960001y
发表时间：
1996
期刊：
Chemical research in toxicology.
影响因子：
--
作者：
Usuki,E;Pearce,R;Parkinson,A;CastagnolJr,N
通讯作者：
CastagnolJr,N