Alpha Lipoic Acid (ALA) Alleviates Hepatocytes Toxicity of Titanium Dioxide Nanoparticles in Rats

The Indonesian Biomedical Journal Pub Date : 2023-06-26 DOI:10.18585/inabj.v15i3.2352

Aiman Al-Maathadi, F. Karawya, Said Al-Dalaen, A. Aljabali, Anas O Satari

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Abstract

BACKGROUND: Titanium dioxide nanoparticles (TiO2 NPs) uptake may primarily cause adverse effects by inducing oxidative stress, resulting in cell damage, genotoxicity, inflammation, and immune response. To date, there are limited studies investigating the adverse effect of TiO2 NPs on liver health and no studies found a naturally occurring compound able to ameliorate such effect. Thus, this study investigated alpha lipoic acid (ALA) potential for reversing the biochemical and histopathological changes that TiO2 NPs exposure causes in rat liver.METHODS: Thirty adult male albino rats were divided into: control rats received distilled water, control rats treated with 50 mg/kg ALA, rats intoxicated with TiO2 NPs, and TiO2 NPs-intoxicated rats treated 50 mg/kg ALA. Rats were sacrificed before blood samples were collected to assess the liver function using parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin and total protein. Liver tissue homogenates were prepared to assess hepatic antioxidant and oxidative stress using parameters of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA). Liver tissue sections were used for histopathological analysis and caspase-3 immunohistochemical analysis.RESULTS: TiO2 NPs produced deleterious effects on rat liver tissue, as confirmed through biochemical results, caspase-3 immunohistochemistry, and histological alterations. TiO2 NPs intoxication induced hepatocyte vacuolation, blood vessels congestion, biliary proliferation, apoptosis, and fibrosis. However, ALA treatment of TiO2 NPs-intoxicated rats significantly alleviated deleterious impact on the liver.CONCLUSION: Administration of 600 mg/kg TiO2 NPs to rats resulted in hepatic degenerative lesions, depletion of GSH, oxidative stress, and apoptosis. However, these changes were mitigated by ALA administration. Therefore, ALA offers protection against deleterious effects of TiO2 NPs intoxication.KEYWORDS: titanium dioxide nanoparticles, TiO2 NPs, hepatotoxicity, alpha-lipoic acid (ALA), rat

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α硫辛酸(ALA)减轻二氧化钛纳米颗粒对大鼠肝细胞的毒性

背景:二氧化钛纳米颗粒(TiO2 NPs)摄取可能主要通过诱导氧化应激引起不良反应，导致细胞损伤、遗传毒性、炎症和免疫反应。迄今为止，研究TiO2 NPs对肝脏健康不利影响的研究有限，没有研究发现一种天然存在的化合物能够改善这种影响。因此，本研究探讨α硫辛酸(ALA)逆转TiO2 NPs暴露引起的大鼠肝脏生化和组织病理学变化的潜力。方法:将30只成年雄性白化大鼠分为:对照组大鼠给予蒸馏水，对照组大鼠给予50 mg/kg ALA, TiO2 NPs中毒大鼠和TiO2 NPs中毒大鼠给予50 mg/kg ALA。取血前处死大鼠，采用谷丙转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素、白蛋白、总蛋白等指标评价肝功能。制备肝组织匀浆，利用超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)和丙二醛(MDA)等参数评估肝脏抗氧化和氧化应激。采用肝组织切片进行组织病理学分析和caspase-3免疫组化分析。结果:通过生化、caspase-3免疫组化和组织学改变证实TiO2 NPs对大鼠肝组织有有害作用。TiO2 NPs中毒引起肝细胞空泡化、血管充血、胆道增生、细胞凋亡和纤维化。然而，ALA处理TiO2 nps中毒大鼠可显著减轻对肝脏的有害影响。结论:600 mg/kg TiO2 NPs可引起大鼠肝脏退行性病变、GSH消耗、氧化应激和细胞凋亡。然而，ALA的管理减轻了这些变化。因此，ALA提供了对TiO2 NPs中毒的有害影响的保护。关键词:二氧化钛纳米颗粒，TiO2 NPs，肝毒性，α -硫辛酸，大鼠

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The Indonesian Biomedical Journal

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