tellurium and Chemical-and-Drug-Induced-Liver-Injury

Topics: Arsenic; Cadmium; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Cobalt; Copper; Gastrointestinal Diseases; Heart Diseases; Humans; Liver; Lung Diseases; Manganese Poisoning; Molybdenum; Nickel; Occupational Medicine; Selenium; Tellurium; Tin; Trace Elements; Vanadium; Zinc

Topics: Cadmium; Cadmium Compounds; Chemical and Drug Induced Liver Injury; Humans; Hydrogen Peroxide; Oxidation-Reduction; Oxidative Stress; Peroxiredoxins; Quantum Dots; Tellurium; Thioredoxins

Quantum dots (QDs), also known as semiconductor QDs, have specific photoelectricproperties which find application in bioimaging, solar cells, and light-emitting diodes (LEDs). However, the application of QDs is often limited by issues related to health risks and potential toxicity. The purpose of this study was to provide evidence regarding the safety of cadmium telluride (CdTe) QDs by exploring the detailed mechanisms involved in its hepatotoxicity. This study showed that CdTe QDs can increase reactive oxygen species (ROS) in hepatocytes after being taken up by hepatocytes, which triggers a significant mitochondrial-dependent apoptotic pathway, leading to hepatocyte apoptosis. CdTe QDs-induce mitochondrial cristae abnormality, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) depolarization. Meanwhile, CdTe QDs can change the morphology, function, and quantity of mitochondria by reducing fission and intimal fusion. Importantly, inhibition of ROS not only protects hepatocyte viability but can also interfere with apoptosis and activation of mitochondrial dysfunction. Similarly, the exposure of CdTe QDs in Institute of Cancer Research (ICR) mice showed that CdTe QDs caused oxidative damage and apoptosis in liver tissue. NAC could effectively remove excess ROS could reduce the level of oxidative stress and significantly alleviate CdTe QDs-induced hepatotoxicity in vivo. CdTe QDs-induced hepatotoxicity may originate from the generation of intracellular ROS, leading to mitochondrial dysfunction and apoptosis, which was potentially regulated by mitochondrial dynamics. This study revealed the nanobiological effects of CdTe QDs and the intricate mechanisms involved in its toxicity at the tissue, cell, and subcellular levels and provides information for narrowing the gap between in vitro and in vivo animal studies and a safety assessment of QDs.

Topics: Animals; Apoptosis; Cadmium Compounds; Chemical and Drug Induced Liver Injury; Mice; Mitochondria; Quantum Dots; Reactive Oxygen Species; Tellurium

Cadmium telluride (CdTe) quantum dots (QDs) can be employed as imaging and drug delivery tools; however, the toxic effects and mechanisms of low-dose exposure are unclear. Therefore, this pioneering study focused on hepatic macrophages (Kupffer cells, KCs) and explored the potential damage process induced by exposure to low-dose CdTe QDs. In vivo results showed that both 2.5 μM/kg·bw and 10 μM/kg·bw could both activate KCs to cause liver injury, and produce inflammation by disturbing antioxidant levels. Abnormal liver function further verified the risks of low-dose exposure to CdTe QDs. The KC model demonstrated that low-dose CdTe QDs (0 nM, 5 nM and 50 nM) can be absorbed by cells and cause severe reactive oxygen species (ROS) production, oxidative stress, and inflammation. Additionally, the expression of NF-κB, caspase-1, and NLRP3 were decreased after pretreatment with ROS scavenging agent N-acetylcysteine (NAC, 5 mM pretreated for 2 h) and the NF-κB nuclear translocation inhibitor Dehydroxymethylepoxyquinomicin (DHMEQ, 10 μg/mL pretreatment for 4 h) respectively. The results indicate that the activation of the NF-κB pathway by ROS not only directly promotes the expression of inflammatory factors such as pro-IL-1β, TNF-α, and IL-6, but also mediates the assembly of NLRP3 by ROS activation of NF-κB pathway, which indirectly promotes the expression of NLRP3. Finally, a high-degree of overlap between the expression of the NF-κB and NLRP3 and the activated regions of KCs, further support the importance of KCs in inflammation induced by low-dose CdTe QDs.

Topics: Cadmium Compounds; Chemical and Drug Induced Liver Injury; Humans; Inflammasomes; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Quantum Dots; Reactive Oxygen Species; Tellurium

Tellurium (Te) is a semiconductor and is frequently doped with copper, tin, gold or silver. It is also used to color glass and ceramics and is one of the primary ingredients in blasting caps. Te is little known about its biological activity but it is well known for toxic to human and animals. It has inhibited the lipids profiles and oxidative stress in the brain of the mice. Sodium tellurite 4.15, 8.3 and 16.6 mg/kg (1/20, 1/10 and 1/5 of LD₅₀, respectively) was given to male Wistar rats orally in saline for a period of 15 days. On day 16, the blood was collected and the livers were dissected out for biochemical assays. The hepatotoxicity biomarkers [biliru- bin, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP)] were ele- vated significantly and dose dependently in the serum of Te treated groups as compared to control group. The content of thiobarbituric acid reactive substances in Te treated groups was increased significantly and dose- dependently as compared to control group. Conversely, the content of glutathione and activities of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase) were decreased significantly in Te treated groups as compared to control group. No data of effect of inorganic Te compounds on the liver toxicity of rats are available. The aim of the present study was to evalu- ate the hepatotoxicity of inorganic Te compounds. In conclusion, Te accelerated hepatotoxicity and oxidative stress in liver tissue of rats.

Topics: Animals; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Male; Oxidative Stress; Rats; Rats, Wistar; Tellurium

The objective of this study was to investigate whether quantum dot 705 (QD705) disrupts the cellular antioxidant systems leading to hepatotoxicity in mice. Mice were intravenously injected with QD705 and then sacrificed at week 12 or 16. Homeostasis of antioxidant-related metals, antioxidant activities, induction of oxidative stress, and toxicity in the liver were investigated. Although no histopathological change was observed, a time- and dose-dependent increase in metallothionein expression and reduction in liver function was noticed. Increased copper, zinc, and selenium levels and enhancements of the trace metal-corresponding transporters were noted at week 12. At week 16, a decline of selenium from its elevated level at week 12 was observed, which was accompanied by changes in glutathione peroxidase activity as well as in redox status. A significant reduction in superoxide dismutase activity was observed at 16 weeks. Furthermore, a corresponding elevation of heme oxygenase-1 expression, 8-oxo-7,8-dihydro-2'-deoxyguanosine, interleukin-6 and tumor necrosis factor-alpha suggested the presence of oxidative stress, oxidative DNA damage and inflammation.

Topics: Animals; Cadmium; Cation Transport Proteins; Chemical and Drug Induced Liver Injury; Cytokines; Gene Expression; Immunohistochemistry; Liver; Male; Metallothionein; Mice; Mice, Inbred ICR; Oxidative Stress; Quantum Dots; Selenium; Superoxide Dismutase; Tellurium