Cadmium and molybdenum co-induce pyroptosis and apoptosis <i>via</i> the PTEN/PI3K/AKT axis in the livers of Shaoxing ducks (<i>Anas platyrhynchos</i>)

Cao, Panpan; Nie, Guoxing; Luo, Junrong; Hu, Ruiming; Li, Guyue; Hu, Guoliang; Zhang, Caiying

doi:10.1039/d1fo02855c

Cited by 31 publications

(16 citation statements)

References 83 publications

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“…Then, we detected the related indices and found that Cd could dramatically up-regulate the expression of IL-18, IL-1β, NLRP3, ASC and caspase-1, and the fluorescence signal of the interaction between NLRP3 and ASC was clearly enhanced, which meant that Cd activated NLRP3 inflammasome. Based on the concentration of Cd in the environment, Cao et al fed ducks with a basal diet containing 4 mg/kg Cd for 16 weeks and the results suggested the expression of NLRP3, ASC, IL-18 and IL-1β was significantly increased, resulting in liver inflammation, which is consistent with our results [ 42 ]. In addition, the co-treatment of Se and Cd could greatly ameliorate the above changes and lower the expression level of NLRP3 inflammasome and other related inflammatory factors.…”

Section: Discussionsupporting

confidence: 90%

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Selenium Antagonizes Cadmium-Induced Inflammation and Oxidative Stress via Suppressing the Interplay between NLRP3 Inflammasome and HMGB1/NF-κB Pathway in Duck Hepatocytes

Cao

Yang

Lin

et al. 2022

IJMS

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Cadmium (Cd) is a toxic heavy metal that can accumulate in the liver of animals, damaging liver function. Inflammation and oxidative stress are considered primary causes of Cd-induced liver damage. Selenium (Se) is an antioxidant and can resist the detrimental impacts of Cd on the liver. To elucidate the antagonism of Se on Cd against hepatocyte injury and its mechanism, duck embryo hepatocytes were treated with Cd (4 μM) and/or Se (0.4 μM) for 24 h. Then, the hepatocyte viability, oxidative stress and inflammatory status were assessed. The findings manifested that the accumulation of reactive oxygen species (ROS) and the levels of pro-inflammatory factors were elevated in the Cd group. Simultaneously, immunofluorescence staining revealed that the interaction between NOD-like receptor pyran domain containing 3 (NLRP3) and apoptosis-associated speck-like protein (ASC) was enhanced, the movement of high-mobility group box 1 (HMGB1) from nucleus to cytoplasm was increased and the inflammatory response was further amplified. Nevertheless, the addition of Se relieved the above-mentioned effects, thereby alleviating cellular oxidative stress and inflammation. Collectively, the results suggested that Se could mitigate Cd-stimulated oxidative stress and inflammation in hepatocytes, which might be correlated with the NLRP3 inflammasome and HMGB1/nuclear factor-κB (NF-κB) signaling pathway.

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Section: Discussionsupporting

confidence: 90%

“…Studies have shown that Cd is hepatotoxic and can cause hepatocyte damage [ 35 , 42 ]. When hepatocytes are damaged, the permeability of the cell membrane increases and the release of LDH and transaminases (ALT and AST) rises, which is an essential indicator for evaluating liver damage [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Selenium Antagonizes Cadmium-Induced Inflammation and Oxidative Stress via Suppressing the Interplay between NLRP3 Inflammasome and HMGB1/NF-κB Pathway in Duck Hepatocytes

Cao

Yang

Lin

et al. 2022

IJMS

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“…They can accumulate after entering the body, and affect the absorption of other trace elements, and finally destroy trace elements balance. Our previous researches confirmed Mo and Cd combined exposure resulted in the distinct increase of Mo and Cd concentrations and decrease the concentrations of Fe, Se, Cu and Zn in duck livers and kidneys 37,38 . In the present study, data verified that Mo or/and Cd obviously elevated their contents in lung, and decreased Cu, Fe, Se and Zn levels and the alteration were most notable in the co‐treated group, further confirming that excess Mo and Cd are cumulative poisons and can lead to the destruction of trace elements homeostasis.…”

Section: Discussionsupporting

confidence: 83%

Molybdenum and cadmium co‐exposure promotesM1macrophage polarization through oxidative stress‐mediated inflammatory response and induces pulmonary fibrosis inShaoxing ducks (Anas platyrhyncha)

Huang

Luo

Guo

et al. 2022

Environmental Toxicology

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High molybdenum (Mo) and cadmium (Cd) are harmful to the body, but pulmonary toxicity induced by Mo and Cd co‐exposure is unknown. To assess the combined impacts of Mo and Cd on fibrosis through M1 polarization in the lung of ducks, 80 healthy 8‐day‐old Shaoxing ducks (Anas platyrhyncha) were randomly assigned to 4 groups and fed with containing unequal doses of Mo or/and Cd diet. Lung tissues were collected on the 16th week. Results indicated that Mo or/and Cd significantly increased their contents in the lungs, and led to trace elements disorder and histological abnormality, and oxidative stress accompanied by promoting contents of H2O2 and MDA and decreasing activities of T‐SOD, GSH‐Px, and CAT, then activated the TLR4/NF‐κB/NLRP3 pathway accompanied by upregulating Caspase‐1, ASC, IL‐18, IL‐1β, TLR4, NF‐κB, and NLRP3 expression levels, and disrupted M1/M2 balance to divert toward M1, which evoked the TGF‐β/Smad2/3‐mediated fibrosis by elevating TGF‐β1, Smad2, Smad3, COL1A1, α‐SMA, and MMP2 expression levels, and decreasing Smad7 and TIMP2 expression levels. The changes of the combined group were most obvious. To sum up, the research demonstrated that Mo or/and Cd may cause macrophages to polarize toward M1 by oxidative stress‐mediated the TLR4/NF‐κB/NLRP3 pathway, then result in fibrosis through the TGF‐β1/Smad2/3 pathway in duck lungs. Mo and Cd may worsen lung damage.

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“…Therefore, Se might inhibit oxidative stress and recover autophagy flux, finally preventing the liver cell pyroptosis. In another study, Cao et al [ 99 ] reported that cadmium and molybdenum induced pyroptosis and apoptosis via PTEN/PI3K/AKT signaling in duck liver tissue; however, the relationship between apoptosis and pyroptosis was not reported, and how autophagy regulated pyroptosis and apoptosis was also not explained. That study suggested that the most important function of PTEN is to block the activation of the PI3K-AKT-m-TOR signaling pathway via its lipid phosphatase activity [ 99 ].…”

Section: The Toxicity Of Cadmium Toward the Kidney Liver Bone And Brainmentioning

confidence: 99%

“…In another study, Cao et al [ 99 ] reported that cadmium and molybdenum induced pyroptosis and apoptosis via PTEN/PI3K/AKT signaling in duck liver tissue; however, the relationship between apoptosis and pyroptosis was not reported, and how autophagy regulated pyroptosis and apoptosis was also not explained. That study suggested that the most important function of PTEN is to block the activation of the PI3K-AKT-m-TOR signaling pathway via its lipid phosphatase activity [ 99 ]. In that study, the results indicated that cadmium induced PTEN activation and inhibited PI3K/AKT signaling, allowing us to speculate that cadmium might promote autophagy development, but prevents autophagy degradation, causing pyroptosis and apoptosis.…”

Section: The Toxicity Of Cadmium Toward the Kidney Liver Bone And Brainmentioning

confidence: 99%

The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity

Yue

et al. 2022

IJMS

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Environmental and occupational exposure to cadmium has been shown to induce kidney damage, liver injury, neurodegenerative disease, and osteoporosis. However, the mechanism by which cadmium induces autophagy in these diseases remains unclear. Studies have shown that cadmium is an effective inducer of oxidative stress, DNA damage, ER stress, and autophagy, which are thought to be adaptive stress responses that allow cells exposed to cadmium to survive in an adverse environment. However, excessive stress will cause tissue damage by inducing apoptosis, pyroptosis, and ferroptosis. Evidently, oxidative stress-induced autophagy plays different roles in low- or high-dose cadmium exposure-induced cell damage, either causing apoptosis, pyroptosis, and ferroptosis or inducing cell survival. Meanwhile, different cell types have different sensitivities to cadmium, which ultimately determines the fate of the cell. In this review, we provided a detailed survey of the current literature on autophagy in cadmium-induced tissue damage. A better understanding of the complex regulation of cell death by autophagy might contribute to the development of novel preventive and therapeutic strategies to treat acute and chronic cadmium toxicity.

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Cadmium and molybdenum co-induce pyroptosis and apoptosis via the PTEN/PI3K/AKT axis in the livers of Shaoxing ducks (Anas platyrhynchos)

Abstract: Cadmium (Cd) and excessive molybdenum (Mo) have adverse impacts on animals. However, the hepatotoxicity co-induced by Cd and Mo in ducks has not been fully elucidated. In order to explore...

Cited by 31 publications

References 83 publications

Selenium Antagonizes Cadmium-Induced Inflammation and Oxidative Stress via Suppressing the Interplay between NLRP3 Inflammasome and HMGB1/NF-κB Pathway in Duck Hepatocytes

Selenium Antagonizes Cadmium-Induced Inflammation and Oxidative Stress via Suppressing the Interplay between NLRP3 Inflammasome and HMGB1/NF-κB Pathway in Duck Hepatocytes

Molybdenum and cadmium co‐exposure promotesM1macrophage polarization through oxidative stress‐mediated inflammatory response and induces pulmonary fibrosis inShaoxing ducks (Anas platyrhyncha)

The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity

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