o:6627 The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis en The mechanism of hepatocyte destruction in chronic hepatitis is not completely understood, while renal failure in individuals with advanced cirrhosis is a significant concern. It is well known that smokers who are chronically infected with hepatitis B and C viruses (HBV, HCV) have a poor prognosis. In the present review, we propose a novel hypothesis that environmental exposure to a nephrotoxic metal pollutant, cadmium (Cd) may contribute to hepatocyte destruction and, subsequently, affect the duration of chronic hepatitis. The metal binding protein, metallothionein (MT) sequesters cadmium as CdMT complexes, and effectively neutralize its adverse effects. Cadmium can cause the damage to hepatocytes, only when it is in an unbound form. In addition to its ability to bind cadmium, MT can act as a scavenger of reactive oxygen species (ROS). However, the cellular MT levels may decrease, when ROS is excessively produced under the pathologic chronic viral hepatitis conditions, especially while the cellular levels of zinc may also be low. Zinc is an endogenous inducer of MT, and is required for maximal MT expression. High ROS levels in the hepatocytes diminishes MT binding to metals. Consequently, the proportion of unbound Cd is increased and thus there is more hepatic damage. Hepatic damage leads to a copious release of CdMT into the circulation. This significant cadmium load, which occurs after hepatic damage, and in some cases, muscle atrophy, induces kidney damage with resultant renal failure in advanced cirrhosis. Cadmium, Chronic hepatitis, Kidney failure, Liver cirrhosis, Metallothionein 1552099 10.1016/j.jtemb.2024.127542 2024-12-17T07:46:08.059Z 44 yes 46 Ana Cirovic Faculty of Medicine, Institute of Anatomy, University of Belgrade The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis Soisungwan Satarug Kidney Disease Research Collaborative, Translational Research Institute, Woolloongabba, Brisbane The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis person Jovan Jevtic Faculty of Medicine, Institute of Pathology, University of Belgrade The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis person Ana Ivanovski Faculty of Medicine, Institute of Pathology, University of Belgrade The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis person Orish E. Orisakwe frican Centre of Excellence for Public Health and Toxicological Research (ACE-PUTOR), University of Port Harcourt The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis person Sasa Jankovic Institute of Meat Hygiene and Technology The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis person 0000-0002-5223-6993 Aleksandar Cirovic Faculty of Medicine, Institute of Anatomy, University of Belgrade, The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis person 2024-10 application/pdf 1986754 https://unilib.phaidrabg.rs/o:6627 no yes 19 70 1552253 71A01 Journal of Trace Elements in Medicine and Biology 127542 86 Elsevier 2024-10