Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney
2014
Аутори
Ivanov, MilanMihailović-Stanojević, Nevena
Grujić-Milanović, Jelica
Jovović, Đurđica
Marković-Lipkovski, Jasmina
Ćirović, Sanja
Miloradović, Zoran
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL an...d lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF.
Извор:
PLoS One, 2014, 9, 5Издавач:
- Public Library Science, San Francisco
Финансирање / пројекти:
- Испитивање антихипертензивног и ренопротективног потенцијала супстанци природног и синтетског порекла у експерименталним моделима кардиоваскуларних и бубрежних обољења (RS-MESTD-Basic Research (BR or ON)-175096)
- Карактеризација бубрежних стем/прогенитор ћелија код човека: идентификација нових површинских маркера мултипотентних бубрежних ћелија које могу имати регенеративну улогу код оштећења бубрега (RS-MESTD-Basic Research (BR or ON)-175047)
DOI: 10.1371/journal.pone.0096353
ISSN: 1932-6203
PubMed: 24796787
WoS: 000336656000066
Scopus: 2-s2.0-84900387612
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Ivanov, Milan AU - Mihailović-Stanojević, Nevena AU - Grujić-Milanović, Jelica AU - Jovović, Đurđica AU - Marković-Lipkovski, Jasmina AU - Ćirović, Sanja AU - Miloradović, Zoran PY - 2014 UR - http://rimi.imi.bg.ac.rs/handle/123456789/560 AB - Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF. PB - Public Library Science, San Francisco T2 - PLoS One T1 - Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney IS - 5 VL - 9 DO - 10.1371/journal.pone.0096353 ER -
@article{ author = "Ivanov, Milan and Mihailović-Stanojević, Nevena and Grujić-Milanović, Jelica and Jovović, Đurđica and Marković-Lipkovski, Jasmina and Ćirović, Sanja and Miloradović, Zoran", year = "2014", abstract = "Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF.", publisher = "Public Library Science, San Francisco", journal = "PLoS One", title = "Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney", number = "5", volume = "9", doi = "10.1371/journal.pone.0096353" }
Ivanov, M., Mihailović-Stanojević, N., Grujić-Milanović, J., Jovović, Đ., Marković-Lipkovski, J., Ćirović, S.,& Miloradović, Z.. (2014). Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney. in PLoS One Public Library Science, San Francisco., 9(5). https://doi.org/10.1371/journal.pone.0096353
Ivanov M, Mihailović-Stanojević N, Grujić-Milanović J, Jovović Đ, Marković-Lipkovski J, Ćirović S, Miloradović Z. Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney. in PLoS One. 2014;9(5). doi:10.1371/journal.pone.0096353 .
Ivanov, Milan, Mihailović-Stanojević, Nevena, Grujić-Milanović, Jelica, Jovović, Đurđica, Marković-Lipkovski, Jasmina, Ćirović, Sanja, Miloradović, Zoran, "Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney" in PLoS One, 9, no. 5 (2014), https://doi.org/10.1371/journal.pone.0096353 . .