Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats
Abstract Indoxyl sulfate (IS), an agonist of aryl hydrocarbon receptors (AhR), can accumulate in patients with chronic kidney disease, but its direct effect on bone is not clear. The present study investigated the effect of chronic exposure to low (100 mg/kg b.w.; 100 IS) and high (200 mg/kg b.w.; 2...
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-53164-3 |
| _version_ | 1797274884102946816 |
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| author | Malgorzata Karbowska Krystyna Pawlak Beata Sieklucka Tomasz Domaniewski Urszula Lebkowska Radoslaw Zawadzki Dariusz Pawlak |
| author_facet | Malgorzata Karbowska Krystyna Pawlak Beata Sieklucka Tomasz Domaniewski Urszula Lebkowska Radoslaw Zawadzki Dariusz Pawlak |
| author_sort | Malgorzata Karbowska |
| collection | DOAJ |
| description | Abstract Indoxyl sulfate (IS), an agonist of aryl hydrocarbon receptors (AhR), can accumulate in patients with chronic kidney disease, but its direct effect on bone is not clear. The present study investigated the effect of chronic exposure to low (100 mg/kg b.w.; 100 IS) and high (200 mg/kg b.w.; 200 IS) dose of IS on bone AhR pathway, sirtuins (SIRTs) expression, oxidative DNA damage and bone mineral status in Wistar rats. The accumulation of IS was observed only in trabecular bone tissue in both doses. The differences were observed in the bone parameters, depending on the applied IS dose. The exposure to 100 IS increased AhR repressor (AhRR)-CYP1A2 gene expression, which was associated with SIRT-1, SIRT-3 and SIRT-7 expression. At the low dose group, the oxidative DNA damage marker was unchanged in the bone samples, and it was inversely related to the abovementioned SIRTs expression. In contrast, the exposure to 200 IS reduced the expression of AhRR, CYP1A, SIRT-3 and SIRT-7 genes compared to 100 IS. The level of oxidative DNA damage was higher in trabecular bone in 200 IS group. Femoral bone mineral density was decreased, and inverse relations were noticed between the level of trabecular oxidative DNA damage and parameters of bone mineral status. In conclusion, IS modulates AhR-depending signaling affecting SIRTs expression, oxidative DNA damage and bone mineral status in a dose dependent manner. |
| first_indexed | 2024-03-07T15:04:33Z |
| format | Article |
| id | doaj.art-a814811de0df473eb93fd94bb71e42ad |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:04:33Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a814811de0df473eb93fd94bb71e42ad2024-03-05T18:58:19ZengNature PortfolioScientific Reports2045-23222024-01-0114111310.1038/s41598-024-53164-3Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in ratsMalgorzata Karbowska0Krystyna Pawlak1Beata Sieklucka2Tomasz Domaniewski3Urszula Lebkowska4Radoslaw Zawadzki5Dariusz Pawlak6Department of Pharmacodynamics, Medical University of BialystokDepartment of Monitored Pharmacotherapy, Medical University of BialystokDepartment of Pharmacodynamics, Medical University of BialystokDepartment of Monitored Pharmacotherapy, Medical University of BialystokDepartment of Radiology, Medical University of BialystokDepartment of Radiology, Medical University of BialystokDepartment of Pharmacodynamics, Medical University of BialystokAbstract Indoxyl sulfate (IS), an agonist of aryl hydrocarbon receptors (AhR), can accumulate in patients with chronic kidney disease, but its direct effect on bone is not clear. The present study investigated the effect of chronic exposure to low (100 mg/kg b.w.; 100 IS) and high (200 mg/kg b.w.; 200 IS) dose of IS on bone AhR pathway, sirtuins (SIRTs) expression, oxidative DNA damage and bone mineral status in Wistar rats. The accumulation of IS was observed only in trabecular bone tissue in both doses. The differences were observed in the bone parameters, depending on the applied IS dose. The exposure to 100 IS increased AhR repressor (AhRR)-CYP1A2 gene expression, which was associated with SIRT-1, SIRT-3 and SIRT-7 expression. At the low dose group, the oxidative DNA damage marker was unchanged in the bone samples, and it was inversely related to the abovementioned SIRTs expression. In contrast, the exposure to 200 IS reduced the expression of AhRR, CYP1A, SIRT-3 and SIRT-7 genes compared to 100 IS. The level of oxidative DNA damage was higher in trabecular bone in 200 IS group. Femoral bone mineral density was decreased, and inverse relations were noticed between the level of trabecular oxidative DNA damage and parameters of bone mineral status. In conclusion, IS modulates AhR-depending signaling affecting SIRTs expression, oxidative DNA damage and bone mineral status in a dose dependent manner.https://doi.org/10.1038/s41598-024-53164-3 |
| spellingShingle | Malgorzata Karbowska Krystyna Pawlak Beata Sieklucka Tomasz Domaniewski Urszula Lebkowska Radoslaw Zawadzki Dariusz Pawlak Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats Scientific Reports |
| title | Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats |
| title_full | Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats |
| title_fullStr | Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats |
| title_full_unstemmed | Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats |
| title_short | Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats |
| title_sort | dose dependent exposure to indoxyl sulfate alters ahr signaling sirtuins gene expression oxidative dna damage and bone mineral status in rats |
| url | https://doi.org/10.1038/s41598-024-53164-3 |
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