Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach
Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration...
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MDPI AG
2022-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/2/402 |
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| author | Matteo Rigato Gianni Carraro Irene Cirella Silvia Dian Valentina Di Vico Lucia Federica Stefanelli Verdiana Ravarotto Giovanni Bertoldi Federico Nalesso Lorenzo A. Calò |
| author_facet | Matteo Rigato Gianni Carraro Irene Cirella Silvia Dian Valentina Di Vico Lucia Federica Stefanelli Verdiana Ravarotto Giovanni Bertoldi Federico Nalesso Lorenzo A. Calò |
| author_sort | Matteo Rigato |
| collection | DOAJ |
| description | Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22<sup>phox</sup> protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22<sup>phox</sup> protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., <i>p</i> = 0.015, vs. 0.53 ± 0.11 d.u., <i>p</i> < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., <i>p</i> = 0.013 and vs. 0.47 ± 0.13 d.u., <i>p</i> < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, <i>p</i> = 0.012, vs. 1.97 ± 1.22 ng/mL, <i>p</i> = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment. |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T01:13:18Z |
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| spelling | doaj.art-8c668b2c561b4ef2bd8cbe278f8a7fb12023-11-23T14:13:24ZengMDPI AGJournal of Clinical Medicine2077-03832022-01-0111240210.3390/jcm11020402Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological ApproachMatteo Rigato0Gianni Carraro1Irene Cirella2Silvia Dian3Valentina Di Vico4Lucia Federica Stefanelli5Verdiana Ravarotto6Giovanni Bertoldi7Federico Nalesso8Lorenzo A. Calò9Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, 35128 Padova, ItalyAutosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22<sup>phox</sup> protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22<sup>phox</sup> protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., <i>p</i> = 0.015, vs. 0.53 ± 0.11 d.u., <i>p</i> < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., <i>p</i> = 0.013 and vs. 0.47 ± 0.13 d.u., <i>p</i> < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, <i>p</i> = 0.012, vs. 1.97 ± 1.22 ng/mL, <i>p</i> = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment.https://www.mdpi.com/2077-0383/11/2/402ADPKDoxidative stresstolvaptan |
| spellingShingle | Matteo Rigato Gianni Carraro Irene Cirella Silvia Dian Valentina Di Vico Lucia Federica Stefanelli Verdiana Ravarotto Giovanni Bertoldi Federico Nalesso Lorenzo A. Calò Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach Journal of Clinical Medicine ADPKD oxidative stress tolvaptan |
| title | Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach |
| title_full | Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach |
| title_fullStr | Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach |
| title_full_unstemmed | Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach |
| title_short | Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach |
| title_sort | effects of tolvaptan on oxidative stress in adpkd a molecular biological approach |
| topic | ADPKD oxidative stress tolvaptan |
| url | https://www.mdpi.com/2077-0383/11/2/402 |
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