1. Academic Validation
  2. Melatonin as a Repairing Agent in Cadmium- and Free Fatty Acid-Induced Lipotoxicity

Melatonin as a Repairing Agent in Cadmium- and Free Fatty Acid-Induced Lipotoxicity

  • Biomolecules. 2023 Dec 7;13(12):1758. doi: 10.3390/biom13121758.
Anna Migni 1 Francesca Mancuso 2 Tiziano Baroni 2 Gabriele Di Sante 2 Mario Rende 2 Francesco Galli 1 Desirée Bartolini 1
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy.
  • 2 Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy.
Abstract

(1) Background: Cadmium (Cd) is a potentially toxic element with a long half-life in the human body (20-40 years). Cytotoxicity mechanisms of Cd include increased levels of oxidative stress and apoptotic signaling, and recent studies have suggested that these aspects of Cd toxicity contribute a role in the pathobiology of non-alcoholic fatty liver disease (NAFLD), a highly prevalent ailment associated with hepatic lipotoxicity and an increased generation of Reactive Oxygen Species (ROS). In this study, Cd toxicity and its interplay with fatty acid (FA)-induced lipotoxicity have been studied in intestinal epithelium and liver cells; the cytoprotective function of melatonin (MLT) has been also evaluated. (2) Methods: human liver cells (HepaRG), primary murine hepatocytes and Caco-2 intestinal epithelial cells were exposed to CdCl2 before and after induction of lipotoxicity with oleic acid (OA) and/or palmitic acid (PA), and in some experiments, FA was combined with MLT (50 nM) treatment. (3) Results: CdCl2 toxicity was associated with ROS induction and reduced cell viability in both the hepatic and intestinal cells. Cd and FA synergized to induce lipid droplet formation and ROS production; the latter was higher for PA compared to OA in liver cells, resulting in a higher reduction in cell viability, especially in HepaRG and primary hepatocytes, whereas CACO-2 cells showed higher resistance to Cd/PA-induced lipotoxicity compared to liver cells. MLT showed significant protection against Cd toxicity either considered alone or combined with FFA-induced lipotoxicity in primary liver cells. (4) Conclusions: Cd and PA combine their pro-oxidant activity to induce lipotoxicity in cellular populations of the gut-liver axis. MLT can be used to lessen the synergistic effect of Cd-PA on cellular ROS formation.

Keywords

cadmium; lipotoxicity; melatonin.

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