title: Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review.
abstract: The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver.
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain. Electronic address: eezubero@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Esteban-Zubero
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Moisés Alejandro
authors.initials: MA
authors.lastname: Alatorre-Jiménez
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Calle Domingo Miral s/n, 50009. Zaragoza, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: López-Pingarrón
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain.
authors.forename: Marcos César
authors.initials: MC
authors.lastname: Reyes-Gonzales
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Almeida-Souza
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Calle Domingo Miral s/n, 50009. Zaragoza, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Cantín-Golet
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Calle Domingo Miral s/n, 50009. Zaragoza, Spain.
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Ruiz-Ruiz
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Dun-Xian
authors.initials: DX
authors.lastname: Tan
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza, Calle Domingo Miral s/n, 50009, Zaragoza, Spain.
authors.forename: José Joaquín
authors.initials: JJ
authors.lastname: García
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: reiter@uthscsa.edu.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
mesh_terms: D000348:Aflatoxins / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D019216:Metals, Heavy / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D009538:Nicotine / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology*; D018805:Sepsis / Q000150:complications*
chemical_list: D000348:Aflatoxins; D000975:Antioxidants; D019216:Metals, Heavy; D020011:Protective Agents; D009538:Nicotine; D002251:Carbon Tetrachloride; D008550:Melatonin
keywords: Chemotherapeutic; Lipid peroxidation; Liver toxicity; Melatonin; Oxidative stress; Sepsis