Ana Cirovic , Soisungwan Satarug , Jovan Jevtic , Ana Ivanovski , Orish E. Orisakwe , Sasa Jankovic , Aleksandar Cirovic
{"title":"被忽视的镉对慢性肝炎进展和晚期肝硬化肾功能衰竭发病的影响","authors":"Ana Cirovic , Soisungwan Satarug , Jovan Jevtic , Ana Ivanovski , Orish E. Orisakwe , Sasa Jankovic , Aleksandar Cirovic","doi":"10.1016/j.jtemb.2024.127542","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127542"},"PeriodicalIF":3.6000,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis\",\"authors\":\"Ana Cirovic , Soisungwan Satarug , Jovan Jevtic , Ana Ivanovski , Orish E. Orisakwe , Sasa Jankovic , Aleksandar Cirovic\",\"doi\":\"10.1016/j.jtemb.2024.127542\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":49970,\"journal\":{\"name\":\"Journal of Trace Elements in Medicine and Biology\",\"volume\":\"86 \",\"pages\":\"Article 127542\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-10-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Trace Elements in Medicine and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0946672X24001627\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Trace Elements in Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0946672X24001627","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis
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.
期刊介绍:
The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods.
Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.