Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury
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 a...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/13/3/370 |
| _version_ | 1827307217450172416 |
|---|---|
| author | Yansheng Li Jiatian Liang Chunyu Jiang Jiawen Cui Lan Hong Zhiyu Hao You Tang Yuhao Liu Xun Cui Xiaohua Teng |
| author_facet | Yansheng Li Jiatian Liang Chunyu Jiang Jiawen Cui Lan Hong Zhiyu Hao You Tang Yuhao Liu Xun Cui Xiaohua Teng |
| author_sort | Yansheng Li |
| collection | DOAJ |
| description | 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 (<i>interleukin (IL)-2</i> and <i>interferon-γ (INF-γ)</i>), and the increase in pro-inflammatory factors (<i>IL-4</i>, <i>IL-6</i>, <i>IL-12β</i>, <i>IL-17</i>, and nitric oxide (NO)). Moreover, we found that the <i>IL-2</i>/<i>IL-17</i>–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 <i>IL-2</i>/<i>IL-17</i>–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–<i>IL-2</i> axis. Interestingly, exposure to Pb inhibited four <i>glutathione peroxidase (GPx)</i> family members (<i>GPx1</i>, <i>GPx2</i>, <i>GPx3</i>, and <i>GPx4</i>), three <i>deiodinase (Dio)</i> family members (<i>Dio1</i>, <i>Dio2</i>, and <i>Dio3</i>), and fifteen other selenoproteins (<i>selenophosphate synthetase 2 (SPS2)</i>, <i>selenoprotein (Sel)H</i>, <i>SelI</i>, <i>SelK</i>, <i>SelM</i>, <i>SelO</i>, <i>SelP1</i>, <i>SelPb</i>, <i>SelS</i>, <i>SelT</i>, <i>SelU</i>, and selenoprotein (Sep)n1, <i>Sepw1</i>, <i>Sepx1</i>, and <i>Sep15</i>), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the <i>SPS2</i>–<i>GPx1</i>–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 <i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–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 <i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–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. |
| first_indexed | 2024-04-24T18:36:38Z |
| format | Article |
| id | doaj.art-5eff107d3c844a4fb2eefd0fc991f970 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-04-24T18:36:38Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-5eff107d3c844a4fb2eefd0fc991f9702024-03-27T13:18:43ZengMDPI AGAntioxidants2076-39212024-03-0113337010.3390/antiox13030370Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory InjuryYansheng Li0Jiatian Liang1Chunyu Jiang2Jiawen Cui3Lan Hong4Zhiyu Hao5You Tang6Yuhao Liu7Xun Cui8Xiaohua Teng9College of Medicine, Yanbian University, Yanji 133002, ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, ChinaCollege of Medicine, Yanbian University, Yanji 133002, ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, ChinaElectrical and Information Engineering College, Jilin Agricultural Science and Technology University, Jilin 132101, ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, ChinaCollege of Medicine, Yanbian University, Yanji 133002, ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, ChinaLead (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 (<i>interleukin (IL)-2</i> and <i>interferon-γ (INF-γ)</i>), and the increase in pro-inflammatory factors (<i>IL-4</i>, <i>IL-6</i>, <i>IL-12β</i>, <i>IL-17</i>, and nitric oxide (NO)). Moreover, we found that the <i>IL-2</i>/<i>IL-17</i>–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 <i>IL-2</i>/<i>IL-17</i>–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–<i>IL-2</i> axis. Interestingly, exposure to Pb inhibited four <i>glutathione peroxidase (GPx)</i> family members (<i>GPx1</i>, <i>GPx2</i>, <i>GPx3</i>, and <i>GPx4</i>), three <i>deiodinase (Dio)</i> family members (<i>Dio1</i>, <i>Dio2</i>, and <i>Dio3</i>), and fifteen other selenoproteins (<i>selenophosphate synthetase 2 (SPS2)</i>, <i>selenoprotein (Sel)H</i>, <i>SelI</i>, <i>SelK</i>, <i>SelM</i>, <i>SelO</i>, <i>SelP1</i>, <i>SelPb</i>, <i>SelS</i>, <i>SelT</i>, <i>SelU</i>, and selenoprotein (Sep)n1, <i>Sepw1</i>, <i>Sepx1</i>, and <i>Sep15</i>), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the <i>SPS2</i>–<i>GPx1</i>–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 <i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–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 <i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–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.https://www.mdpi.com/2076-3921/13/3/370leadseleniumselenoproteinsoxidative stressinflammation<i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–NO pathway |
| spellingShingle | Yansheng Li Jiatian Liang Chunyu Jiang Jiawen Cui Lan Hong Zhiyu Hao You Tang Yuhao Liu Xun Cui Xiaohua Teng Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury Antioxidants lead selenium selenoproteins oxidative stress inflammation <i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–NO pathway |
| title | Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury |
| title_full | Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury |
| title_fullStr | Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury |
| title_full_unstemmed | Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury |
| title_short | Se Alleviated Pb-Caused Neurotoxicity in Chickens: <i>SPS2</i>-<i>GPx1</i>-GSH-<i>IL-2</i>/<i>IL-17</i>-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury |
| title_sort | se alleviated pb caused neurotoxicity in chickens i sps2 i i gpx1 i gsh i il 2 i i il 17 i no pathway selenoprotein suppression oxidative stress and inflammatory injury |
| topic | lead selenium selenoproteins oxidative stress inflammation <i>SPS2</i>–<i>GPx1</i>–GSH–<i>IL-2</i>/<i>IL-17</i>–NO pathway |
| url | https://www.mdpi.com/2076-3921/13/3/370 |
| work_keys_str_mv | AT yanshengli sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT jiatianliang sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT chunyujiang sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT jiawencui sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT lanhong sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT zhiyuhao sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT youtang sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT yuhaoliu sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT xuncui sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury AT xiaohuateng sealleviatedpbcausedneurotoxicityinchickensisps2iigpx1igshiil2iiil17inopathwayselenoproteinsuppressionoxidativestressandinflammatoryinjury |