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N-乙酰半胱氨酸脂质体纳米颗粒对百草枯诱导的雄性大鼠肾毒性的保护作用

Protective Effects of N-acetylcysteine Niosome Nanoparticles on Paraquatinduced Nephrotoxicity in Male Rats.

作者信息

Jouzdani Ali Fathi, Ganjirad Zahra, Firozian Farzin, Soleimani-Asl Sara, Ranjbar Akram

机构信息

Student Research Committee, Hamadan University of Medical Science, Hamadan, Iran.

Department of Pharmaceutics, Faculty of Pharmacy, Hamadan University of Medical Science, Hamadan, Iran.

出版信息

Pharm Nanotechnol. 2022;10(2):137-145. doi: 10.2174/2211738510666220214102034.

Abstract

INTRODUCTION

Paraquat (PQ), as a bipyridyl compound, is widely used as an effective herbicide that produces reactive oxygen species (ROS), affecting the unsaturated lipids of cell membranes leading to cell mortality. N-acetylcysteine (NAC) is a medication that has a beneficial role in reducing the intoxication of kidneys caused by PQ. Niosomes are bilayer vesicles that enhance the bioavailability of drugs. This study aimed to compare the effects of NAC and niosome of NAC (NACNPs) on PQ-induced kidney toxicity concerning its antioxidant activity.

METHODS

In this experimental study, after formulating NACNP, 30 Wistar male rats weighing 180 to 250 gm were classified into five groups: the control group was treated with normal saline, while the other four groups received 35mg/kg/day of PQ via intraperitoneal route and, was treated with 25mg/kg/day NAC, 25mg/kg/day niosome and 25 mg/kg/day NACNP by gavage, Then, oxidative stress biomarkers such as total antioxidant capacity (TAC), catalase activity (CAT), lipid peroxidation (LPO), and total thiol group (TTG), plus blood urea nitrogen (BUN) and creatinine levels were evaluated in kidney tissue homogenate and examined histopathologically.

RESULTS

The results revealed that TTG increased significantly in NAC & NACNP groups than in the PQ group. Further, in the PQ group, LPO increased significantly compared with the control, NAC, and NACNP groups, while in the NAC and NACNP group, LPO diminished compared with the PQ group. There was no significant difference in TAC between groups. Blood urea nitrogen (BUN) and creatinine levels dropped in NACNP compared with the PQ group and the NAC. Histological studies also approved PQ-induced damage and the protective effect of NACNP.

CONCLUSION

The results indicated that NACNP could modulate oxidative stress status and kidney function against PQ toxicity.

摘要

引言

百草枯(PQ)作为一种联吡啶化合物,被广泛用作有效的除草剂,它会产生活性氧(ROS),影响细胞膜的不饱和脂质,导致细胞死亡。N-乙酰半胱氨酸(NAC)是一种药物,在减轻PQ引起的肾脏中毒方面具有有益作用。脂质体是可提高药物生物利用度的双层囊泡。本研究旨在比较NAC和NAC脂质体(NACNPs)对PQ诱导的肾脏毒性及其抗氧化活性的影响。

方法

在本实验研究中,制备NACNP后,将30只体重180至250克的Wistar雄性大鼠分为五组:对照组用生理盐水处理,而其他四组通过腹腔注射接受35mg/kg/天的PQ,并通过灌胃分别用25mg/kg/天的NAC、25mg/kg/天的脂质体和25mg/kg/天的NACNP进行处理。然后,在肾脏组织匀浆中评估氧化应激生物标志物,如总抗氧化能力(TAC)、过氧化氢酶活性(CAT)、脂质过氧化(LPO)和总巯基(TTG),以及血尿素氮(BUN)和肌酐水平,并进行组织病理学检查。

结果

结果显示,NAC和NACNP组的TTG显著高于PQ组。此外,与对照组、NAC组和NACNP组相比,PQ组的LPO显著升高,而在NAC和NACNP组中,LPO较PQ组降低。各组之间TAC无显著差异。与PQ组和NAC组相比,NACNP组的血尿素氮(BUN)和肌酐水平下降。组织学研究也证实了PQ诱导的损伤以及NACNP的保护作用。

结论

结果表明,NACNP可以调节氧化应激状态并保护肾脏功能免受PQ毒性的影响。

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