Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues
Cristina Anna Gallelli,
Silvio Calcagnini,
Adele Romano,
Justyna Barbara Koczwara,
Marialuisa de Ceglia,
Donatella Dante,
Rosanna Villani,
Anna Maria Giudetti,
Tommaso Cassano,
Silvana Gaetani
Affiliations
Cristina Anna Gallelli
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Silvio Calcagnini
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Adele Romano
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Justyna Barbara Koczwara
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Marialuisa de Ceglia
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Donatella Dante
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Rosanna Villani
C.U.R.E. University Centre for Liver Disease Research and Treatment, Department of Medical and Surgical Sciences, Institute of Internal Medicine, University of Foggia, 71122 Foggia, Italy
Anna Maria Giudetti
Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, 73100 Lecce, Italy
Tommaso Cassano
Department of Clinical and Experimental Medicine, University of Foggia, Via Luigi Pinto, c/o Ospedali Riuniti, 71122 Foggia, Italy
Silvana Gaetani
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Growing evidence supports the pivotal role played by oxidative stress in tissue injury development, thus resulting in several pathologies including cardiovascular, renal, neuropsychiatric, and neurodegenerative disorders, all characterized by an altered oxidative status. Reactive oxygen and nitrogen species and lipid peroxidation-derived reactive aldehydes including acrolein, malondialdehyde, and 4-hydroxy-2-nonenal, among others, are the main responsible for cellular and tissue damages occurring in redox-dependent processes. In this scenario, a link between the endocannabinoid system (ECS) and redox homeostasis impairment appears to be crucial. Anandamide and 2-arachidonoylglycerol, the best characterized endocannabinoids, are able to modulate the activity of several antioxidant enzymes through targeting the cannabinoid receptors type 1 and 2 as well as additional receptors such as the transient receptor potential vanilloid 1, the peroxisome proliferator-activated receptor alpha, and the orphan G protein-coupled receptors 18 and 55. Moreover, the endocannabinoids lipid analogues N-acylethanolamines showed to protect cell damage and death from reactive aldehydes-induced oxidative stress by restoring the intracellular oxidants-antioxidants balance. In this review, we will provide a better understanding of the main mechanisms triggered by the cross-talk between the oxidative stress and the ECS, focusing also on the enzymatic and non-enzymatic antioxidants as scavengers of reactive aldehydes and their toxic bioactive adducts.
