Biomedical Sciences Department, College of Medicine, Gulf Medical University, Ajman, 4184, UAE.
Department of Pharmacotherapeutics, College of Pharmacy, Immam Abdulrahman University, 8273, Dmmam, Saudi Arabia.
J Mol Histol. 2024 Nov 30;56(1):17. doi: 10.1007/s10735-024-10311-4.
The current investigation was designed as an experimental endeavor to explore the protective efficacy of dehydroepiandrosterone (DHEA) and quercetin against hepatotoxicity induced by copper oxide (CuO) nanoparticles. Rats were subjected to CuO nanoparticle intoxication through intraperitoneal injection of 150 mg/kg b.w. for three weeks, followed by the administration of the aforementioned antioxidants for an additional three weeks. This study systematically tracked alterations in liver enzymatic activity, antioxidant levels, apoptotic markers, and histopathological changes using the comet assay. CuO nanoparticle-intoxicated rats exhibited a significant increase in serum alanine transaminase aspartate aminotransferase (AST), and bilirubin levels, coupled with a noteworthy reduction in serum albumin. Moreover, there was a marked rise in serum tumor necrosis factor-alpha levels, concomitant with a significant decline in serum hepatocyte growth factor (HGF). Caspase-3 and Bax mRNA levels in the serum showed a substantial increase, while serum Bcl-2 mRNA levels witnessed a significant decrease. Liver tissue levels of malondialdehyde (MDA) and nitric oxide (NOx) experienced a significant elevation, and DNA damage was observed through the comet assay. Histopathological examination of the liver tissue substantiated these aforementioned findings. Administration of the antioxidants DHEA or quercetin, either individually or in combination, mitigated the parameters of hepatotoxicity to varying extents. In summary, the hepatic genotoxicity induced by CuO nanoparticles demonstrated improvement following the administration of either DHEA or quercetin. Additionally, their combined administration exhibited a more potent protective potential.
本研究旨在通过实验探索脱氢表雄酮(DHEA)和槲皮素对氧化铜(CuO)纳米粒子诱导的肝毒性的保护作用。实验采用腹腔注射 150mg/kg bw 的 CuO 纳米粒子对大鼠进行染毒,持续 3 周,然后再给予上述抗氧化剂治疗 3 周。本研究采用彗星试验系统地跟踪了肝酶活性、抗氧化水平、凋亡标志物和组织病理学变化。结果显示,CuO 纳米粒子染毒大鼠血清丙氨酸氨基转移酶(AST)、天冬氨酸氨基转移酶(ALT)和胆红素水平显著升高,血清白蛋白显著降低。此外,血清肿瘤坏死因子-α(TNF-α)水平显著升高,而血清肝细胞生长因子(HGF)水平显著降低。血清 caspase-3 和 Bax mRNA 水平显著升高,而血清 Bcl-2 mRNA 水平显著降低。肝组织丙二醛(MDA)和一氧化氮(NOx)水平显著升高,彗星试验检测到 DNA 损伤。肝组织的组织病理学检查证实了上述发现。抗氧化剂 DHEA 或槲皮素单独或联合给药在不同程度上减轻了肝毒性的参数。综上所述,CuO 纳米粒子诱导的肝遗传毒性在给予 DHEA 或槲皮素后得到改善。此外,两者联合给药表现出更强的保护潜力。