Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD
Background/Objectives: Chronic kidney disease (CKD) is a progressive pathological condition which results in the severe fibrosis of the kidneys. However, the mechanisms of CKD progression and fibrogenesis remain unclear. We wanted to examine the effects that apocynin and hyperbaric oxygen therapy (H...
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2024-12-01
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| author | Andrija Vukovic Danijela Karanovic Nevena D Mihailovic-Stanojevic Zoran Miloradovic Predrag Brkic Maja Zivotic Jelena Nesovic Ostojic Milan Ivanov Sanjin Kovacevic Una-Jovana Vajic Djurdjica Jovovic Silvio R. De Luka |
| author_facet | Andrija Vukovic Danijela Karanovic Nevena D Mihailovic-Stanojevic Zoran Miloradovic Predrag Brkic Maja Zivotic Jelena Nesovic Ostojic Milan Ivanov Sanjin Kovacevic Una-Jovana Vajic Djurdjica Jovovic Silvio R. De Luka |
| author_sort | Andrija Vukovic |
| collection | DOAJ |
| description | Background/Objectives: Chronic kidney disease (CKD) is a progressive pathological condition which results in the severe fibrosis of the kidneys. However, the mechanisms of CKD progression and fibrogenesis remain unclear. We wanted to examine the effects that apocynin and hyperbaric oxygen therapy (HBOT) have on renal function and structure in animals with CKD induced through 5/6 nephrectomy (5/6 Nx-L). Methods: Male Wistar rats were divided in 5 groups (n = 8/group) as follows: control—sham-operated rats; Nx-L—rats with 5/6 Nx-L; APO—5/6 Nx-L + apocynin treatment; HBOT—5/6 Nx-L + hyperbaric oxygen treatment, and APO+HBOT—5/6 Nx-L, treated with both treatments. All treatments started 4 weeks after the final step of CKD induction and lasted for 4 weeks. At the end of the experiment, urine samples were collected for the proteinuria assessment and the mean arterial pressure (MAP) was measured. Kidneys were collected for histopathological, Western blot, and immunohistochemical analyses. Results: All treatments significantly decreased MAP compared to the Nx-L group (<i>p</i> < 0.001). In the APO and APO+HBOT groups, the level of proteinuria was decreased compared to the Nx-L group (<i>p</i> < 0.05 and <i>p</i> < 0.01, respectively). All examined treatments significantly decreased the intensity of lesions in the kidney compared to those observed in the Nx-L group (<i>p</i> < 0.001). Isolated treatments with apocynin and HBOT induced a significant decrease in desmin expression compared to the Nx-L group (<i>p</i> < 0.05); meanwhile, they did not affect the levels of fibronectin (FN) and hypoxia-inducible factor-1α (HIF-1α). Combined treatment did not affect desmin expression levels; however, it induced a significant increase in fibronectin expression compared to Nx-L (<i>p</i> < 0.001). Conclusions: Apocynin treatment decreased BP and protein loss, and it improved renal morphology at least partly through the downregulation of desmin expression without changing FN and HIF-1α. Hyperbaric oxygen therapy improved hypertension but failed to significantly affect the level of proteinuria. Combined treatment (apocynin and HBOT) normalized blood pressure (BP) values, renal function, and improved kidney structure by modulating FN and HIF-1α, without affecting desmin protein expression. Further studies are needed to elucidate the mechanisms of slowing down the progression of CKD in this experimental model. |
| format | Article |
| id | doaj-art-e64d91c965014328849d26f5c246dfe1 |
| institution | DOAJ |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-e64d91c965014328849d26f5c246dfe12025-08-20T02:53:43ZengMDPI AGBiomedicines2227-90592024-12-011212278810.3390/biomedicines12122788Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKDAndrija Vukovic0Danijela Karanovic1Nevena D Mihailovic-Stanojevic2Zoran Miloradovic3Predrag Brkic4Maja Zivotic5Jelena Nesovic Ostojic6Milan Ivanov7Sanjin Kovacevic8Una-Jovana Vajic9Djurdjica Jovovic10Silvio R. De Luka11Institute of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotića 1, 11000 Belgrade, SerbiaInstitute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, SerbiaInstitute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, SerbiaInstitute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, SerbiaInstitute of Medical Physiology, Faculty of Medicine, University of Belgrade, Višegradska 26, 11000 Belgrade, SerbiaInstitute of Pathology, Faculty of Medicine, University of Belgrade, Dr Subotića 1, 11000 Belgrade, SerbiaInstitute of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotića 1, 11000 Belgrade, SerbiaInstitute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, SerbiaInstitute of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotića 1, 11000 Belgrade, SerbiaInstitute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, SerbiaInstitute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, SerbiaInstitute of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotića 1, 11000 Belgrade, SerbiaBackground/Objectives: Chronic kidney disease (CKD) is a progressive pathological condition which results in the severe fibrosis of the kidneys. However, the mechanisms of CKD progression and fibrogenesis remain unclear. We wanted to examine the effects that apocynin and hyperbaric oxygen therapy (HBOT) have on renal function and structure in animals with CKD induced through 5/6 nephrectomy (5/6 Nx-L). Methods: Male Wistar rats were divided in 5 groups (n = 8/group) as follows: control—sham-operated rats; Nx-L—rats with 5/6 Nx-L; APO—5/6 Nx-L + apocynin treatment; HBOT—5/6 Nx-L + hyperbaric oxygen treatment, and APO+HBOT—5/6 Nx-L, treated with both treatments. All treatments started 4 weeks after the final step of CKD induction and lasted for 4 weeks. At the end of the experiment, urine samples were collected for the proteinuria assessment and the mean arterial pressure (MAP) was measured. Kidneys were collected for histopathological, Western blot, and immunohistochemical analyses. Results: All treatments significantly decreased MAP compared to the Nx-L group (<i>p</i> < 0.001). In the APO and APO+HBOT groups, the level of proteinuria was decreased compared to the Nx-L group (<i>p</i> < 0.05 and <i>p</i> < 0.01, respectively). All examined treatments significantly decreased the intensity of lesions in the kidney compared to those observed in the Nx-L group (<i>p</i> < 0.001). Isolated treatments with apocynin and HBOT induced a significant decrease in desmin expression compared to the Nx-L group (<i>p</i> < 0.05); meanwhile, they did not affect the levels of fibronectin (FN) and hypoxia-inducible factor-1α (HIF-1α). Combined treatment did not affect desmin expression levels; however, it induced a significant increase in fibronectin expression compared to Nx-L (<i>p</i> < 0.001). Conclusions: Apocynin treatment decreased BP and protein loss, and it improved renal morphology at least partly through the downregulation of desmin expression without changing FN and HIF-1α. Hyperbaric oxygen therapy improved hypertension but failed to significantly affect the level of proteinuria. Combined treatment (apocynin and HBOT) normalized blood pressure (BP) values, renal function, and improved kidney structure by modulating FN and HIF-1α, without affecting desmin protein expression. Further studies are needed to elucidate the mechanisms of slowing down the progression of CKD in this experimental model.https://www.mdpi.com/2227-9059/12/12/2788CKDapocyninhyperbaric oxygen therapy5/6 nephrectomyfibrosisdesmin |
| spellingShingle | Andrija Vukovic Danijela Karanovic Nevena D Mihailovic-Stanojevic Zoran Miloradovic Predrag Brkic Maja Zivotic Jelena Nesovic Ostojic Milan Ivanov Sanjin Kovacevic Una-Jovana Vajic Djurdjica Jovovic Silvio R. De Luka Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD Biomedicines CKD apocynin hyperbaric oxygen therapy 5/6 nephrectomy fibrosis desmin |
| title | Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD |
| title_full | Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD |
| title_fullStr | Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD |
| title_full_unstemmed | Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD |
| title_short | Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD |
| title_sort | apocynin and hyperbaric oxygen therapy improve renal function and structure in an animal model of ckd |
| topic | CKD apocynin hyperbaric oxygen therapy 5/6 nephrectomy fibrosis desmin |
| url | https://www.mdpi.com/2227-9059/12/12/2788 |
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