Cadmium Through Disturbing MTF1-Mediated Metal Response Induced Cerebellar Injury

Bi, Shao-Shuai; Talukder, Milton; Jin, Hong; Lv, Mei-Wei; Ge, Jing; Zhang, Cong; Li, Jinlong

doi:10.1007/s12640-022-00474-x

Cited by 7 publications

(4 citation statements)

References 58 publications

(60 reference statements)

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“…Histopathological observation of cerebral tissues using H&E staining was performed as previously described our studies. , In brief, small pieces of cerebral tissues (4 mm) were fixed in 10% neutral buffered formalin for 24 h and processed for H&E staining. Furthermore, Nissl staining was performed to confirm the histopathological alterations in the cerebral tissues.…”

Section: Methodsmentioning

confidence: 99%

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1

Talukder

et al. 2023

J. Agric. Food Chem.

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Cadmium (Cd) is a hazardous environmental metal that poses a global public health concern due to its high toxic potential. Nanoselenium (Nano-Se) is a nanoform of elemental Se that is widely used to antagonize heavy metal toxicity owing to its high safety margin with low doses. However, the role of Nano-Se in relieving Cd-induced brain damage is unclear. For this study, Cd-exposure-induced cerebral damage was established by using a chicken model. Administration of Nano-Se with Cd significantly decreased the Cd-mediated elevation of cerebral ROS, MDA, and H 2 O 2 levels as well as markedly increased the Cd-mediated reduced activities of antioxidant biomarkers (GPX, T-SOD, CAT, and T-AOC). Accordingly, co-treatment with Nano-Se significantly reduced Cd-mediated increased Cd accumulation and recovered the Cd-induced biometal imbalance, notably Se and Zn. Nano-Se downregulated the Cd-induced upregulation of ZIP8, ZIP10, ZNT3, ZNT5, and ZNT6 and upregulated the Cdmediated decreased expressions of ATOX1 and XIAP. Nano-Se also increased the Cd-mediated decreased mRNA levels of MTF1 and its target genes MT1 and MT2. Surprisingly, co-treatment with Nano-Se regulated the Cd-induced increased total protein level of MTF1 by reducing its expression. Moreover, altered selenoproteins regulation was recovered after co-treatment with Nano-Se as evidenced by increased expression levels of antioxidant selenoproteins (GPx1−4 and SelW) and Se transport-related selenoproteins (SepP1 and SepP2). The histopathological evaluation and Nissl staining of the cerebral tissues also supported that Nano-Se markedly reduced the Cd-induced microstructural alterations and well preserved the normal histological architectures of the cerebral tissue. Overall, the results of this research reveal that Nano-Se may be beneficial in mitigating Cd-induced cerebral injury in the brains of chickens. This present study provides a basis for preclinical research for its usefulness as a potential therapeutic for the treatment of neurodegeneration in the heavy-metal-induced neurotoxicity.

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Section: Methodsmentioning

confidence: 99%

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1

Talukder

et al. 2023

J. Agric. Food Chem.

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“…Under Pb treatment conditions, two GPx family members (GPx1 and GPx4), SelK, and Sep15 were down-regulated in mouse livers [ 21 ], as well as four GPx family members (GPx1-4), three Dio family members (Dio1-3), SPS2, SelH, SelI, SelK, SelM, SelO, SelS, SelT, SelU, SelP1, SelPb, Sepn1, Sepx1, and Sep15, declined in chicken brainstems [ 22 ]. A recent study confirmed that Cd resulted in abnormal selenoprotein mRNA levels (three GPx family members (GPx1-3), SelH, SelI, SelK, SelM, SelO, SelS, SelT, SelP1, Sepx1, and Sep15 were decreased) in chicken Ces [ 17 ]. However, to the best of our knowledge, there is no research on the effect of Pb on the above 22 selenoproteins in Ces and Thi.…”

Section: Introductionmentioning

confidence: 96%

“…Oxidative stress and tissue lesions in Thi occurred in chickens receiving excess copper and arsenic, and glutathione (GSH) and total antioxidant capacity (TAC) decreased, while malondialdehyde (MDA) increased [ 16 ]. Cd poisoning led to oxidative stress with elevated MDA and tissue damage in chicken Ces [ 17 ]. Hence, we inferred that Pb can down-regulate GSH and TAC, up-regulate MDA, and lead to oxidative stress in chicken Ces and Thi.…”

Section: Introductionmentioning

confidence: 99%

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury

Li,

Liang,

Jiang

et al. 2024

Antioxidants

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Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12β, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17–NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17–NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH–IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2–GPx1–GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2–GPx1–GSH–IL-2/IL-17–NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2–GPx1–GSH–IL-2/IL-17–NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.

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“…In the area of toxicological study, Cd toxicity is a crucial public health concern. Nano-Se is a vital trace element, which has anticancer and antioxidant properties, for both human and animal health. − It has been proven in numerous previous investigations to have a mitigating impact on the toxicity of heavy metals − and also have a beneficial role in protection against free radicals, neurobiology, muscle metabolism, reproduction, and liver damage. , However, it is unclear whether it can attenuate Cd-induced liver pyroptosis and also liver fibrosis. Furthermore, studies have demonstrated that when the liver is affected by toxic substances, hepatocytes will produce NLRP3 inflammasomes, which are then released into liver stellate cells, leading to liver fibrosis .…”

Section: Introductionmentioning

confidence: 99%

Nano-Selenium Antagonized Cadmium-Induced Liver Fibrosis in Chicken

Sun

Zhao

et al. 2022

J. Agric. Food Chem.

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Cadmium is a global ecological toxic pollutant; in animals, hepatotoxic fibrosis is caused by bioaccumulation of Cd through food chains. We determined the path of nano-Se antagonism in Cd-induced hepatocyte pyroptosis by targeting the APJ-AMPK-PGC1α pathway, using an in vivo model of hepatotoxicity. All 1-day-old chicks were treated with Cd (140 mg/kg BW/day) and/or nano-Se (0.3 or 0.6 mg/kg BW/day) for 90 days. The result showed that Cd (1.55 ± 0.148) activated NLRP3 inflammasome 49.903% as compared to the Con group (1.034 ± 0.008) to release the inflammasome as a result of hepatocyte pyroptosis (2.824 ± 0.057). Compared with the Con group (1.010 ± 0.021), Kupffer cells were 219.109% more to activate astrocytes through the APJ-AMPK-PGC1α pathway, resulting in 185.149% more hepatic fibrosis. However, the fibrosis degree of the H-Se + Cd group (1.252 ± 0.056) was 56.5278% (p < 0.001) lower than that of the Cd group (2.880 ± 0.124). Therefore, this study established that pyroptotic hepatocytes and Kupffer cells could be targeted for nano-Se antagonizing Cd toxicity, which reveals a potential new approach targeting astrocytes for the treatment of liver fibrosis triggered by Cd pollution.

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Cadmium Through Disturbing MTF1-Mediated Metal Response Induced Cerebellar Injury

Cited by 7 publications

References 58 publications

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury

Nano-Selenium Antagonized Cadmium-Induced Liver Fibrosis in Chicken

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