Thallium(I and III) exposure leads to liver damage and disorders of fatty acid metabolism in mice

Li, Dong; Yao, Huan; Du, Lei; Zeng, Xianyin; Xiao, Qihai

doi:10.1016/j.chemosphere.2022.135618

Cited by 12 publications

(7 citation statements)

References 46 publications

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“…Mechanistically, experimental studies suggest that the liver is the storage site of thallium and hepatic mitochondria as one of the most important targets of the thallium liver injury [210]. Thallium exposure to animals caused impaired mitochondrial fatty acid metabolism [211]. Isolated mitochondria treated with thallium in vitro exhibited marked elevation in oxidative stress parameters, accompanied by increased mitochondrial ROS generation, adenosine triphosphate (ATP) depletion, impaired oxidation of reduced glutathione (GSH), and mitochondrial membrane potential (MMP) collapse [210].…”

Section: Thalliummentioning

confidence: 99%

Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps

Teschke

Xuan

2022

Front. Biosci. (Landmark Ed)

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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 1 O2, 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.

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Section: Thalliummentioning

confidence: 99%

Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps

Teschke

Xuan

2022

Front. Biosci. (Landmark Ed)

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“…Cyl-CoA Dehydrogenase Medium Chain ( ACADM ) catalyzes the β-oxidation of medium-chain fatty acids [ 32 ], and the deficiency of this gene can cause fatty acid metabolism disorders and liver function abnormalities [ 33 ]. 3-Hydroxy-3-Methylglutaryl-CoA synthase 2 ( HMGCS2 ) provides lipid-derived energy to hepatocytes, and up-regulated expression of the HMGCS2 gene is associated with fatty acid oxidation induced by high-fat diets [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Transcriptome Profiling Reveals the Mechanisms Underlying Hepatic Metabolism under Different Raising Systems in Yak

Zhang,

Zha,

et al. 2024

Animals

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Yak meat is nutritionally superior to beef cattle but has a low fat content and is slow-growing. The liver plays a crucial role in lipid metabolism, and in order to determine whether different feeding modes affect lipid metabolism in yaks and how it is regulated, we employed RNA sequencing (RNA-seq) technology to analyze the genome-wide differential gene expression in the liver of yaks maintained under different raising systems. A total of 1663 differentially expressed genes (DEGs) were identified (|log2FC| ≥ 0 and p-value ≤ 0.05), including 698 down-regulated and 965 up-regulated genes. According to gene ontology (GO) and KEGG enrichment analyses, these DEGs were significantly enriched in 13 GO terms and 26 pathways (p < 0.05). Some DEGs were enriched in fatty acid degradation, PPAR, PI3K-Akt, and ECM receptor pathways, which are associated with lipid metabolism. A total of 16 genes are well known to be related to lipid metabolism (e.g., APOA1, FABP1, EHHADH, FADS2, SLC27A5, ACADM, CPT1B, ACOX2, HMGCS2, PLIN5, ACAA1, IGF1, FGFR4, ALDH9A1, ECHS1, LAMA2). A total of 11 of the above genes were significantly enriched in the PPAR signaling pathway. The reliability of the transcriptomic data was verified using qRT-PCR. Our findings provide new insights into the mechanisms regulating yak meat quality. It shows that fattening improves the expression of genes that regulate lipid deposition in yaks and enhances meat quality. This finding will contribute to a better understanding of the various factors that determine yak meat quality and help develop strategies to improve yield and quality.

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“…Thallium (Tl) administration results in experimental liver injury because the liver is the preferred site of its storage, and hepatic mitochondria are the most important target subcellular organelles within the hepatocytes for the Tl injury [ 96 ], as evidenced by impaired mitochondrial fatty acid metabolism [ 97 ]. Isolated mitochondria treated with Tl in vitro exhibited marked elevation in oxidative stress parameters, accompanied by increased mitochondrial ROS generation, adenosine triphosphate (ATP) depletion, impaired oxidation of reduced glutathione (GSH), and mitochondrial membrane potential (MMP) collapse [ 96 ].…”

Section: Thalliummentioning

confidence: 99%

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

Teschke

2022

IJMS

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Experimental liver injury with hepatocelluar necrosis and abnormal liver tests is caused by exposure to heavy metals (HMs) like aluminum, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, mercury, molybdenum, nickel, platinum, thallium, titanium, vanadium, and zinc. As pollutants, HMs disturb the ecosystem, and as these substances are toxic, they may affect the health of humans and animals. HMs are not biodegradable and may be deposited preferentially in the liver. The use of animal models can help identify molecular and mechanistic steps leading to the injury. HMs commonly initiate hepatocellular overproduction of ROS (reactive oxygen species) due to oxidative stress, resulting in covalent binding of radicals to macromolecular proteins or lipids existing in membranes of subcellular organelles. Liver injury is facilitated by iron via the Fenton reaction, providing ROS, and is triggered if protective antioxidant systems are exhausted. Ferroptosis syn pyroptosis was recently introduced as mechanistic concept in explanations of nickel (Ni) liver injury. NiCl2 causes increased iron deposition in the liver, upregulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, downregulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), nuclear receptor coactivator 4 (NCOA4) protein, and mRNA expression levels. Nickel may cause hepatic injury through mitochondrial damage and ferroptosis, defined as mechanism of iron-dependent cell death, similar to glutamate-induced excitotoxicity but likely distinct from apoptosis, necrosis, and autophagy. Under discussion were additional mechanistic concepts of hepatocellular uptake and biliary excretion of mercury in exposed animals. For instance, the organic anion transporter 3 (Oat3) and the multidrug resistance-associated protein 2 (Mrp2) were involved in the hepatic handling of mercury. Mercury treatment modified the expression of Mrp2 and Oat3 as assessed by immunoblotting, partially explaining its impaired biliary excretion. Concomitantly, a decrease in Oat3 abundance in the hepatocyte plasma membranes was observed that limits the hepatic uptake of mercury ions. Most importantly and shown for the first time in liver injury caused by HMs, titanium changed the diversity of gut microbiota and modified their metabolic functions, leading to increased generation of lipopolysaccharides (LPS). As endotoxins, LPS may trigger and perpetuate the liver injury at the level of gut-liver. In sum, mechanistic and molecular steps of experimental liver injury due to HM administration are complex, with ROS as the key promotional compound. However, additional concepts such as iron used in the Fenton reaction, ferroptosis, modification of transporter systems, and endotoxins derived from diversity of intestinal bacteria at the gut-liver level merit further consideration.

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Thallium(I and III) exposure leads to liver damage and disorders of fatty acid metabolism in mice

Cited by 12 publications

References 46 publications

Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps

Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps

Genome-Wide Transcriptome Profiling Reveals the Mechanisms Underlying Hepatic Metabolism under Different Raising Systems in Yak

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

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