5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway
Sodium ferrous citrate (SFC) is involved in the metabolism of 5-aminolevulinic acid (5-ALA) and enhances its anti-inflammatory effects. The effects of 5-ALA/SFC on inflammation in rats with endotoxin-induced uveitis (EIU) have yet to be elucidated. In this study, during lipopolysaccharide injection,...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8653 |
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| author | Yuya Otaka Kazutaka Kanai Arisa Mori Daiki Okada Noriaki Nagai Yohei Yamashita Yoichiro Ichikawa Kazuki Tajima |
| author_facet | Yuya Otaka Kazutaka Kanai Arisa Mori Daiki Okada Noriaki Nagai Yohei Yamashita Yoichiro Ichikawa Kazuki Tajima |
| author_sort | Yuya Otaka |
| collection | DOAJ |
| description | Sodium ferrous citrate (SFC) is involved in the metabolism of 5-aminolevulinic acid (5-ALA) and enhances its anti-inflammatory effects. The effects of 5-ALA/SFC on inflammation in rats with endotoxin-induced uveitis (EIU) have yet to be elucidated. In this study, during lipopolysaccharide injection, 5-ALA/SFC (10 mg/kg 5-ALA plus 15.7 mg/kg SFC) or 5-ALA (10 or 100 mg/kg) was administered via gastric gavage, wherein we saw that 5-ALA/SFC ameliorated ocular inflammation in EIU rats by suppressing clinical scores; by infiltrating cell counts, aqueous humor protein, and inflammatory cytokine levels; and by improving histopathological scores to the same extent as 100 mg/kg 5-ALA. Immunohistochemistry showed that 5-ALA/SFC suppressed iNOS and COX-2 expression, NF-κB activation, IκB-α degradation, and p-IKKα/β expression, and activated HO-1 and Nrf2 expression. Therefore, this study has investigated how 5-ALA/SFC reduces inflammation and revealed the pathways involved in EIU rats. 5-ALA/SFC is shown to inhibit ocular inflammation in EIU rats by inhibiting NF-κB and activating the HO-1/Nrf2 pathways. |
| first_indexed | 2024-03-11T03:40:16Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:16Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1bdff86f9bf94aff8b9d5b5c49a4bcc02023-11-18T01:39:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410865310.3390/ijms241086535-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling PathwayYuya Otaka0Kazutaka Kanai1Arisa Mori2Daiki Okada3Noriaki Nagai4Yohei Yamashita5Yoichiro Ichikawa6Kazuki Tajima7Department of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanDepartment of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanDepartment of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanDepartment of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanFaculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, JapanDepartment of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanDepartment of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanDepartment of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University, 35-1 Higashi-23ban-cho, Towada 034-8628, Aomori, JapanSodium ferrous citrate (SFC) is involved in the metabolism of 5-aminolevulinic acid (5-ALA) and enhances its anti-inflammatory effects. The effects of 5-ALA/SFC on inflammation in rats with endotoxin-induced uveitis (EIU) have yet to be elucidated. In this study, during lipopolysaccharide injection, 5-ALA/SFC (10 mg/kg 5-ALA plus 15.7 mg/kg SFC) or 5-ALA (10 or 100 mg/kg) was administered via gastric gavage, wherein we saw that 5-ALA/SFC ameliorated ocular inflammation in EIU rats by suppressing clinical scores; by infiltrating cell counts, aqueous humor protein, and inflammatory cytokine levels; and by improving histopathological scores to the same extent as 100 mg/kg 5-ALA. Immunohistochemistry showed that 5-ALA/SFC suppressed iNOS and COX-2 expression, NF-κB activation, IκB-α degradation, and p-IKKα/β expression, and activated HO-1 and Nrf2 expression. Therefore, this study has investigated how 5-ALA/SFC reduces inflammation and revealed the pathways involved in EIU rats. 5-ALA/SFC is shown to inhibit ocular inflammation in EIU rats by inhibiting NF-κB and activating the HO-1/Nrf2 pathways.https://www.mdpi.com/1422-0067/24/10/8653HO-1lipopolysaccharideNrf2NF-κBsodium ferrous citrateuveitis |
| spellingShingle | Yuya Otaka Kazutaka Kanai Arisa Mori Daiki Okada Noriaki Nagai Yohei Yamashita Yoichiro Ichikawa Kazuki Tajima 5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway International Journal of Molecular Sciences HO-1 lipopolysaccharide Nrf2 NF-κB sodium ferrous citrate uveitis |
| title | 5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway |
| title_full | 5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway |
| title_fullStr | 5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway |
| title_full_unstemmed | 5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway |
| title_short | 5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway |
| title_sort | 5 ala sfc ameliorates endotoxin induced ocular inflammation in rats by inhibiting the nf κb signaling pathway and activating the ho 1 nrf2 signaling pathway |
| topic | HO-1 lipopolysaccharide Nrf2 NF-κB sodium ferrous citrate uveitis |
| url | https://www.mdpi.com/1422-0067/24/10/8653 |
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