The Protective Effect of α-Lipoic Acid against Gold Nanoparticles (AuNPs)-Mediated Liver Damage Is Associated with Upregulating Nrf2 and Suppressing NF-κB

• Published in: Nutrients 2022-08, Vol.14 (16), p.3327
• Main Authors: Alshammari, Ghedeir M, Abdelhalim, Mohamed Anwar, Al-Ayed, Mohammed S, Al-Harbi, Laila Naif, Yahya, Mohammed Abdo
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Animals; Antioxidants; Apoptosis; Aspartate; Aspartate aminotransferase; B-cell lymphoma; BAX protein; Care and treatment; Caspase-3; Catalase; Cytokines; Degeneration; Development and progression; Gold; gold nanoparticles; Health aspects; Heme; Heme oxygenase (decyclizing); hepatotoxicity; Inflammation; Interleukin 6; Interleukins; Lipoic acid; Liver; Liver diseases; Lymphocytes B; Lymphoma; Lymphomas; mRNA; Nanoparticles; NF-κB protein; Oxidative stress; Oxygenase; Physiological aspects; Proteins; Risk factors; RNA; Serum levels; Superoxide; Superoxide dismutase; Transaminases; Transcription factors; Tumor necrosis factor; Tumor necrosis factor-α; Vitamin E; α-lipoic acid; γ-Glutamyltransferase
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14163327

This study examined if regulating the keap-1? Nrf2 antioxidant pathway mediated gold nanoparticles (AuNPs) induced liver damage, and examined the protective effect of co-supplement of α-lipoic acid (α-LA). Rats were separated into 4 groups (n = 8/each) as control, α-LA (200 mg/kg), AuNPs (5 µg/2.85 × 1011), and AuNPs (5 µg/2.85 × 1011) + α-LA (200 mg/kg). After 7 days, AuNPs induced severe degeneration in the livers of rats with the appearance of some fatty changes. In addition, it increased serum levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (ɣ-GTT), and aspartate aminotransferase (AST), as well as liver levels of malondialdehyde (MDA). Concomitantly, AuNPs significantly depleted hepatic levels of total glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) but increased hepatic levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). It also reduced mRNA levels of B-cell lymphoma 2 (Bcl2) and heme oxygenase-1 (HO-1) but significantly increased those of Bax and cleaved caspase-3, as well as the ratio of Bax/Bcl2. In addition, AuNPs enhanced the total and nuclear levels of NF-κB p65 but reduced the mRNA and total and nuclear protein levels of Nrf2. Of note, AuNPs did not affect the mRNA levels of keap-1. All these events were reversed by α-LA in the AuNPs-treated rats. In conclusion, α-LA attenuated AuNPs-mediated liver damage in rats by suppressing oxidative stress and inflammation, effects that are associated with upregulation/activation of Nrf2.