Role of Autophagy in Cadmium-Induced Hepatotoxicity and Liver Diseases

Abstract

Cadmium (Cd) is a toxic pollutant that is associated with several severe human diseases. Cd can be easily absorbed in significant quantities from air contamination/industrial pollution, cigarette smoke, food, and water and primarily affects the liver, kidney, and lungs. Toxic effects of Cd include hepatotoxicity, nephrotoxicity, pulmonary toxicity, and the development of various human cancers. Cd is also involved in the development and progression of fatty liver diseases and hepatocellular carcinoma. Cd affects liver function via modulation of cell survival/proliferation, differentiation, and apoptosis. Moreover, Cd dysregulates hepatic autophagy, an endogenous catabolic process that detoxifies damaged cell organelles or dysfunctional cytosolic proteins through vacuole-mediated sequestration and lysosomal degradation. In this article, we review recent developments and findings regarding the role of Cd in the modulation of hepatotoxicity, autophagic function, and liver diseases at the molecular level.

Heavy Metal Accumulation, Tissue Injury, Oxidative Stress, and Inflammation in Dromedary Camels Living near Petroleum Industry Sites in Saudi Arabia

“…Cd can negatively affect the antioxidant system via its ability to bind the thiol group of the antioxidant enzymes [58], and inhibit complex III of the mitochondrial electron transport chain [58]. Kidney injury manifested by glomerular degeneration has been observed in rodents exposed to Cd [59], and hepatotoxicity and several liver diseases are serious effects of exposure to this HM [60]. The toxic effects of Ni are associated with increased ROS, MDA, and NO levels, mitochondrial dysfunction, and swelling in the ovaries of rats [61].…”

Mechanisms of Cadmium-Induced Testicular Injury: A Risk to Male Fertility

“…Cadmium promotes lysosomal acidification in vivo and in vitro by inducing the lysosomal-associated membrane protein 2 (LAMP2) and the lysosomal hydrolase cathepsin B and increases lysosomal degradation potential. However, cadmium suppresses Rab7 protein expression, resulting in defective fusion of the autophagosomes with lysosomes [ 130 , 131 ]. Cadmium concentration elevated the expression of the autophagy proteins LC3B, Beclin1, sequestosome 1 (SQSTM1/p62), and its autophagy active form LC3B-II in the testis.…”

Aluminum, Arsenic, Beryllium, Cadmium, Chromium, Cobalt, Copper, Iron, Lead, Mercury, Molybdenum, Nickel, Platinum, Thallium, Titanium, Vanadium, and Zinc: Molecular Aspects in Experimental Liver Injury

“…The associated lipid peroxidation was obviously triggered by iron released from biological membranes [ 35 ]. In detail, the toxic Cd 2+ was bound to the protein metallothionenin (MT) to form the Cd metallothionenin (Cd-MT) complex [ 37 ]. This facilitated hepatic cadmium deposition and downgraded glutathione production, accompanied with increased ROS production through oxidative stress and mitochondrial injury.…”

“…Impaired mitochondrial functions led to metabolic-associated fatty liver disease (MAFLD) due to lipid deposition in the liver. In the further course of events, metabolic-associated steatohepatitis steatosis (MASH) may develop [ 37 ].…”