Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis
Acetaminophen (APAP)-induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00660/full |
| _version_ | 1818034388137410560 |
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| author | Zheng Ge Chenyu Wang Junjie Zhang Xiwang Li Junhong Hu |
| author_facet | Zheng Ge Chenyu Wang Junjie Zhang Xiwang Li Junhong Hu |
| author_sort | Zheng Ge |
| collection | DOAJ |
| description | Acetaminophen (APAP)-induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with a single dose of tempol (20 mg/kg per day) orally for 7 days. On the seventh day, mice were injected with a single dose of APAP (300 mg/kg) to induce acute hepatotoxicity. Our results showed that tempol treatment markedly improved liver functions with alleviations of histopathological damage induced by APAP. Tempol treatment upregulated levels of antioxidant proteins, including superoxide dismutase, catalase, and glutathione. Also, phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) and protein expression of nuclear factor erythroid 2-related factor (Nrf 2) and heme oxygense-1 (HO-1) were all increased by tempol, which indicated tempol protected against APAP-induced hepatotoxicity via the PI3K/Akt/Nrf2 pathway. Moreover, tempol treatment decreased pro-apoptotic protein expressions (cleaved caspase-3 and Bax) and increased anti-apoptotic Bcl-2 in liver, as well as reducing apoptotic cells of TUNEL staining, which suggested apoptotic effects of tempol treatment. Overall, we found that tempol normalizes liver function in APAP-induced acute hepatotoxicity mice via activating PI3K/Akt/Nrf2 pathway, thus enhancing antioxidant response and inhibiting hepatic apoptosis. |
| first_indexed | 2024-12-10T06:38:22Z |
| format | Article |
| id | doaj.art-03d18b8f7a114151955713df4078036f |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T06:38:22Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-03d18b8f7a114151955713df4078036f2022-12-22T01:58:50ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-05-011010.3389/fphys.2019.00660457667Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and ApoptosisZheng GeChenyu WangJunjie ZhangXiwang LiJunhong HuAcetaminophen (APAP)-induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with a single dose of tempol (20 mg/kg per day) orally for 7 days. On the seventh day, mice were injected with a single dose of APAP (300 mg/kg) to induce acute hepatotoxicity. Our results showed that tempol treatment markedly improved liver functions with alleviations of histopathological damage induced by APAP. Tempol treatment upregulated levels of antioxidant proteins, including superoxide dismutase, catalase, and glutathione. Also, phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) and protein expression of nuclear factor erythroid 2-related factor (Nrf 2) and heme oxygense-1 (HO-1) were all increased by tempol, which indicated tempol protected against APAP-induced hepatotoxicity via the PI3K/Akt/Nrf2 pathway. Moreover, tempol treatment decreased pro-apoptotic protein expressions (cleaved caspase-3 and Bax) and increased anti-apoptotic Bcl-2 in liver, as well as reducing apoptotic cells of TUNEL staining, which suggested apoptotic effects of tempol treatment. Overall, we found that tempol normalizes liver function in APAP-induced acute hepatotoxicity mice via activating PI3K/Akt/Nrf2 pathway, thus enhancing antioxidant response and inhibiting hepatic apoptosis.https://www.frontiersin.org/article/10.3389/fphys.2019.00660/fullacetaminophenacute hepatotoxicitytempoloxidative stressapoptosis |
| spellingShingle | Zheng Ge Chenyu Wang Junjie Zhang Xiwang Li Junhong Hu Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis Frontiers in Physiology acetaminophen acute hepatotoxicity tempol oxidative stress apoptosis |
| title | Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis |
| title_full | Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis |
| title_fullStr | Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis |
| title_full_unstemmed | Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis |
| title_short | Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis |
| title_sort | tempol protects against acetaminophen induced acute hepatotoxicity by inhibiting oxidative stress and apoptosis |
| topic | acetaminophen acute hepatotoxicity tempol oxidative stress apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00660/full |
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