Pathology Department, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza, Egypt.
Biochemistry Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Sci Rep. 2022 Jun 15;12(1):9986. doi: 10.1038/s41598-022-13960-1.
Widespread application of carbendazim (CBZ) is a major environmental impact because of its residues that caused multi-organ dysfunction. Recently, Chitosan nanoparticles (CS-NPs) are extensively used as nanocarriers due to their non-toxic and biodegradable nature. Therefore, the current study aimed to investigate the possible mechanistic pathway of modified CS-NPs to reduce the hepatic and nephrotoxicity of CBZ in rats. CS-NPs were synthesized by the ionic gelation method by using ascorbic acid instead of acetic acid to increase its antioxidant efficiency. Twenty-adult male Wistar rats were grouped (n = 5) as follows: Group (1) negative control, group (2) received CS-NPs, group (3) received CBZ, and group (4) co-administered CS-NPs with CBZ. Rats received the aforementioned materials daily by oral gavage for 28 days and weighed weekly. The results revealed that CBZ receiving group showed severe histopathological alterations in the liver and kidney sections including cellular necrosis and interstitial inflammation confirmed by immunostaining and showed marked immunopositivity of iNOS and caspase-3 protein. There were marked elevations in the serum levels of ALT, AST, urea, and creatinine with a significant increase in MDA levels and decrease in TAC levels. Upregulation of the Keap1 gene and down-regulation of Nrf2 and HO-1 genes were also observed. Co-treatment of rats by CS-NPs with CBZ markedly improved all the above-mentioned toxicological parameters and return liver and kidney tissues to normal histological architecture. We concluded that CBZ caused hepatorenal toxicity via oxidative stress and the Nrf2/HO-1 pathway and CS-NPs could reduce CBZ toxicity via their antioxidant, anti-apoptotic, and anti-inflammatory effects.
广泛应用多菌灵（CBZ）会造成多器官功能障碍，是一个主要的环境影响因素，因为其残留。最近，由于壳聚糖纳米粒子（CS-NPs）具有无毒和可生物降解的性质，因此被广泛用作纳米载体。因此，本研究旨在探讨改性 CS-NPs 降低 CBZ 在大鼠肝和肾毒性的可能机制途径。CS-NPs 通过离子凝胶化法合成，使用抗坏血酸代替乙酸以提高其抗氧化效率。将 20 只成年雄性 Wistar 大鼠分为 5 组（n = 5）：组 1 为阴性对照组，组 2 给予 CS-NPs，组 3 给予 CBZ，组 4 给予 CS-NPs 与 CBZ 共同给药。大鼠每天通过口服灌胃接受上述材料 28 天，并每周称重。结果表明，CBZ 组大鼠肝和肾组织出现严重的组织病理学改变，包括细胞坏死和间质炎症，免疫染色证实，并显示 iNOS 和 caspase-3 蛋白的免疫阳性。血清 ALT、AST、尿素和肌酐水平显著升高，MDA 水平显著升高，TAC 水平显著降低。Keap1 基因上调，Nrf2 和 HO-1 基因下调。用 CS-NPs 与 CBZ 共同处理大鼠，明显改善了所有上述毒理学参数，并使肝和肾组织恢复正常的组织学结构。我们得出结论，CBZ 通过氧化应激和 Nrf2/HO-1 途径引起肝肾功能障碍，CS-NPs 可通过其抗氧化、抗凋亡和抗炎作用降低 CBZ 毒性。
