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壳聚糖-三聚磷酸钠包封的槲皮素纳米颗粒:通过全面的体内研究揭示其对乙硫磷诱导的发育毒性的增强保护机制及阐释

Chitosan-TPP encapsulated quercetin nanoparticles: amplified protection mechanisms unveiled against Ethion-induced developmental toxicity through comprehensive in-vivo and elucidation.

作者信息

Ranjith D, Telang A G, Subhadra Sandhya, Kamothi Dhaval J, Madhu C L, Kumar Dinesh

机构信息

Division of Pharmacology and Toxicology, ICAR- Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India.

Toxicology Laboratory, Centre for Animal Disease Research and Diagnosis (CADRAD), ICAR- Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, India.

出版信息

Toxicol Res (Camb). 2024 May 17;13(3):tfae074. doi: 10.1093/toxres/tfae074. eCollection 2024 Jun.

Abstract

AIM

The study investigated Ethion-induced developmental toxicity in Wistar albino rats and the potential ameliorative effects of quercetin and nano-quercetin co-administration. Further, In-silico docking of Ethion and quercetin with MCL-1 was conducted.

METHODOLOGY

Quercetin nanoparticles were synthesized by ionic-gelation method. The encapsulated quercetin nanoparticles were characterized for Zeta size, UV-Vis spectroscopy, encapsulation efficiency, and TEM studies. Male rats were administered Ethion (high/low dose), quercetin, and nano-quercetin alone or in combination for 60 days. Female rats were introduced for mating on the 61st day, and pregnant females were observed for 20 gestational days. On GD 20, rats were sacrificed and evaluated for body/organ weight, reproductive indices, fetal morphology, skeletal, and visceral deformities.In silico binding energies of ethion and quercetin with MCL-1 were determined.

RESULTS

Nanoparticle size was 363.2 ± 1.23 nm on day 0 and 385.63 ± 1.53 nm on day 60, with PDI of 0.247 and charge of 22.9 mV. Absorbance maxima were at 374 nm, with encapsulation efficacy of 85.16 ± 0.33%. EHD male crossed females showed decreased body/organ weights, reduced fertility, hematoma, cleft palate, tail curling, and absence of extremity. Nano-quercetin co-administration normalized parameters comparable to controls. Both Ethion and quercetin interacted with MCL-1, with quercetin exhibiting stronger binding energy.

CONCLUSION

Nano-quercetin demonstrated stronger antioxidant properties than quercetin, counteracting ethion-induced maternal/fetal abnormalities.

摘要

目的

本研究调查了乙硫磷对Wistar白化大鼠的发育毒性以及槲皮素和纳米槲皮素联合给药的潜在改善作用。此外,还进行了乙硫磷和槲皮素与MCL-1的计算机模拟对接。

方法

采用离子凝胶法合成槲皮素纳米颗粒。对包封的槲皮素纳米颗粒进行了zeta尺寸、紫外可见光谱、包封效率和透射电镜研究。雄性大鼠单独或联合给予乙硫磷(高/低剂量)、槲皮素和纳米槲皮素60天。在第61天引入雌性大鼠进行交配,并观察怀孕雌性大鼠20天的妊娠期。在妊娠第20天,处死大鼠并评估其体重/器官重量、生殖指标、胎儿形态、骨骼和内脏畸形情况。测定了乙硫磷和槲皮素与MCL-1的计算机模拟结合能。

结果

第0天纳米颗粒尺寸为363.2±1.23nm,第60天为385.63±1.53nm,多分散指数为0.247,电荷为22.9mV。最大吸光度在374nm处,包封率为85.16±0.33%。乙硫磷雄性与雌性杂交后,大鼠体重/器官重量下降、生育力降低、出现血肿、腭裂、尾巴卷曲和肢体缺失。纳米槲皮素联合给药使各项参数恢复正常,与对照组相当。乙硫磷和槲皮素均与MCL-1相互作用,槲皮素表现出更强的结合能。

结论

纳米槲皮素比槲皮素具有更强的抗氧化性能,可抵消乙硫磷诱导的母体/胎儿异常。

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