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Effects of captopril, telmisartan and bardoxolone methyl ( CDDO ‐Me) in ischemia‐reperfusion‐induced acute kidney injury in rats: an experimental comparative study
Author(s) -
Kocak Cengiz,
Kocak Fatma Emel,
Akcilar Raziye,
Bayat Zeynep,
Aras Bekir,
Metineren Mehmet Huseyin,
Yucel Mehmet,
Simsek Hasan
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12511
Subject(s) - nitric oxide synthase , chemistry , asymmetric dimethylarginine , renal ischemia , telmisartan , kidney , endocrinology , malondialdehyde , enos , medicine , creatinine , lipocalin , pharmacology , nitric oxide , glutathione peroxidase , superoxide dismutase , reperfusion injury , oxidative stress , ischemia , biochemistry , arginine , amino acid , blood pressure
Summary 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 ‐ κ B) 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 ‐ κ B, 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 ( DDAH s) 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.