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- Title
Effects of captopril, telmisartan and bardoxolone methyl ( CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.
- Authors
Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Bayat, Zeynep; Aras, Bekir; Metineren, Mehmet Huseyin; Yucel, Mehmet; Simsek, Hasan
- Abstract
Renal ischemia-reperfusion ( IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril ( CAP), telmisartan ( TEL) and bardoxolone methyl ( BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin ( NGAL) levels, tissue total oxidant status ( TOS), total antioxidant status ( TAS), total thiol ( TT), asymmetric dimethylarginine ( ADMA) levels, superoxide dismutase ( SOD) activity and glutathione peroxidase ( GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-ɣ ( PPAR-ɣ), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells ( NF- κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide ( NO) and ADMA levels, NF- κB, inducible nitric oxide synthase ( iNOS) and endothelin-1 ( ET-1) expressions ( P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase ( eNOS) expression, dimethylarginine dimethylaminohydrolases ( DDAHs) expression, Nrf2 expression and PPAR-ɣ expression ( P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects.
- Subjects
KIDNEY injuries; TREATMENT of reperfusion injuries; CAPTOPRIL; ANGIOTENSIN receptors; TRITERPENOIDS; ANTIOXIDANTS; APOPTOSIS prevention; THERAPEUTICS
- Publication
Clinical & Experimental Pharmacology & Physiology, 2016, Vol 43, Issue 2, p230
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12511