IMR Press / FBL / Volume 27 / Issue 11 / DOI: 10.31083/j.fbl2711314
Open Access Review
Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps
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1 Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, D-63450 Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, Frankfurt/Main, Germany
2 Center for the Planetary Health and Innovation Science (PHIS), The IDEC Institute, Hiroshima University, 739-8529 Higashi-Hiroshima, Japan
*Correspondence: (Rolf Teschke)
Academic Editor: Vesna Jacevic
Front. Biosci. (Landmark Ed) 2022, 27(11), 314;
Submitted: 7 September 2022 | Revised: 30 October 2022 | Accepted: 16 November 2022 | Published: 25 November 2022
(This article belongs to the Special Issue Hepatotoxicity: Molecular Mechanisms and Pathophysiology)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Aluminum, arsenic, cadmium, chromium, cobalt, copper, iron, lead, mercury, nickel, thallium, titanium, zinc, carbon tetrachloride, phthalates, glyphosate, alcohol, drugs, and herbs are under discussion having the potential to injure the human liver, but allocation of the injury to the hepatotoxicant as exact cause is difficult for physicians and requires basic clinical knowledge of toxicology details. Liver injury occurs at a variable extent depending on the dose, mostly reproducible in animal models that allow studies on molecular steps leading to the hepatocellular injury. These exogenous hepatotoxins may cause an overproduction of reactive oxidative species (ROS), which are generated during microsomal or mitochondrial oxidative stress from incomplete oxygen split and trigger the injury if protective antioxidant capacities are reduced. Primary subcelluar target organelles involved are liver mitochondria through lipid peroxidation of membrane structures and the action of free radicals such as singlet radical 1O2, superoxide radical HO•2, hydrogen peroxide H2O2, hydroxyl radical HO•, alkoxyl radical RO•, and peroxyl radical ROO•. They attempt covalent binding to macromolecular structural proteins. As opposed to inorganic chemicals, liver injury due to chemicals with an organic structure proceedes via the hepatic microsomal cytochrome P450 with its different isoforms. In sum, many exogenous chemicals may have the potential of liver injury triggerd by overproduced ROS leading primarily to impairment of mitochondial functions in the course of structural mitochondial membrane dearrangement. As clinical data were often incomplete, future clinical prototols should focus on meeting liver injury criteria, exclusion of alternative causes, a robust causality evaluation management, and obtaining liver histology if clinically indicated and of benefit for the patient.

heavy metals
carbon tetrachloride
Fig. 1.
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