Curcumin ameliorates lead-induced hepatotoxicity by suppressing oxidative stress and inflammation, and modulating akt/gsk-3β signaling pathway

Ahlam Alhusaini, Laila Fadda, Iman H. Hasan, Enas Zakaria, Abeer M. Alenazi, Ayman M. Mahmoud

Research output: Contribution to journalJournal articlepeer-review

21 Scopus citations

Abstract

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.

Original languageEnglish
Article number703
JournalBiomolecules
Volume9
Issue number11
DOIs
StatePublished - Nov 2019
Externally publishedYes

Keywords

  • Curcumin
  • GSK-3β
  • JNK
  • Lead
  • NF-κB
  • Oxidative stress

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