Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats
Bisphenol A (BPA), extensively utilized in the manufacture of epoxy resins and polycarbonate plastics, is prevalent in the environment. Its exposure has been associated with an increased risk of hepatic lesions; however, the underlying mechanisms and the spectrum of its effects remain poorly underst...
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2024-11-01
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| author | Juan Tang Kai Wang Dan Shen Chunmei Li |
| author_facet | Juan Tang Kai Wang Dan Shen Chunmei Li |
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| description | Bisphenol A (BPA), extensively utilized in the manufacture of epoxy resins and polycarbonate plastics, is prevalent in the environment. Its exposure has been associated with an increased risk of hepatic lesions; however, the underlying mechanisms and the spectrum of its effects remain poorly understood. This study investigates the role of the Keap1-Nrf2 signaling pathway in regulating BPA-induced hepatotoxicity in vivo using a rat model. Over a 30-day period, rats were orally administered either corn oil or BPA (0.5, 5, and 50 mg/kg). Changes in hepatic and kidney histology were assessed via transmission electron microscopy and HE staining. Oxidative stress levels in the liver tissue and serum were quantified, while the mRNA expression of <i>Nrf2</i>, <i>Keap1</i>, <i>GPX2</i>, <i>HO-1</i>, and <i>caspase-3</i> was evaluated using qRT-PCR. Additionally, the expression of Nrf2 and cleaved caspase-3 in the liver tissue was measured through immunohistochemistry and Western blotting. Results indicated that BPA exposure significantly reduced the liver and adrenal coefficients in the treated rats compared to controls. Notable histomorphological alterations were observed in the liver and kidney tissues of the BPA-treated rats. The serum levels of GOT and TNF-α were significantly elevated in the BPA group relative to the controls. Evidence of oxidative stress was supported by increased malondialdehyde levels and decreased total superoxide dismutase activity in the liver and kidney, alongside a reduction in glutathione peroxidase activity in the liver tissue. Furthermore, BPA exposure enhanced the mRNA expression levels of <i>Nrf2</i>, <i>Keap1</i>, <i>GPX2</i>, <i>HO-1</i>, and <i>caspase-3</i> in the liver tissue. Concurrently, Nrf2 and cleaved caspase-3 expression levels were elevated in the BPA-treated group compared to the controls. These findings suggest that BPA may contribute to metabolic disorders of liver function and poses a hepatotoxicity risk. Moreover, the activation of the Keap1-Nrf2 pathway may offer protective effects against hepatotoxicity, with potential implications for human liver disease. |
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| institution | Kabale University |
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| publishDate | 2024-11-01 |
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| series | Toxics |
| spelling | doaj-art-5a73c2c23e5644c9acb08f1bfb62b99d2024-12-27T14:56:38ZengMDPI AGToxics2305-63042024-11-01121286410.3390/toxics12120864Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in RatsJuan Tang0Kai Wang1Dan Shen2Chunmei Li3College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaBisphenol A (BPA), extensively utilized in the manufacture of epoxy resins and polycarbonate plastics, is prevalent in the environment. Its exposure has been associated with an increased risk of hepatic lesions; however, the underlying mechanisms and the spectrum of its effects remain poorly understood. This study investigates the role of the Keap1-Nrf2 signaling pathway in regulating BPA-induced hepatotoxicity in vivo using a rat model. Over a 30-day period, rats were orally administered either corn oil or BPA (0.5, 5, and 50 mg/kg). Changes in hepatic and kidney histology were assessed via transmission electron microscopy and HE staining. Oxidative stress levels in the liver tissue and serum were quantified, while the mRNA expression of <i>Nrf2</i>, <i>Keap1</i>, <i>GPX2</i>, <i>HO-1</i>, and <i>caspase-3</i> was evaluated using qRT-PCR. Additionally, the expression of Nrf2 and cleaved caspase-3 in the liver tissue was measured through immunohistochemistry and Western blotting. Results indicated that BPA exposure significantly reduced the liver and adrenal coefficients in the treated rats compared to controls. Notable histomorphological alterations were observed in the liver and kidney tissues of the BPA-treated rats. The serum levels of GOT and TNF-α were significantly elevated in the BPA group relative to the controls. Evidence of oxidative stress was supported by increased malondialdehyde levels and decreased total superoxide dismutase activity in the liver and kidney, alongside a reduction in glutathione peroxidase activity in the liver tissue. Furthermore, BPA exposure enhanced the mRNA expression levels of <i>Nrf2</i>, <i>Keap1</i>, <i>GPX2</i>, <i>HO-1</i>, and <i>caspase-3</i> in the liver tissue. Concurrently, Nrf2 and cleaved caspase-3 expression levels were elevated in the BPA-treated group compared to the controls. These findings suggest that BPA may contribute to metabolic disorders of liver function and poses a hepatotoxicity risk. Moreover, the activation of the Keap1-Nrf2 pathway may offer protective effects against hepatotoxicity, with potential implications for human liver disease.https://www.mdpi.com/2305-6304/12/12/864bisphenol AhepatotoxicityHO-1Nrf2rat |
| spellingShingle | Juan Tang Kai Wang Dan Shen Chunmei Li Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats Toxics bisphenol A hepatotoxicity HO-1 Nrf2 rat |
| title | Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats |
| title_full | Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats |
| title_fullStr | Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats |
| title_full_unstemmed | Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats |
| title_short | Oxidative Stress and Keap1-Nrf2 Pathway Involvement in Bisphenol A-Induced Liver Damage in Rats |
| title_sort | oxidative stress and keap1 nrf2 pathway involvement in bisphenol a induced liver damage in rats |
| topic | bisphenol A hepatotoxicity HO-1 Nrf2 rat |
| url | https://www.mdpi.com/2305-6304/12/12/864 |
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