title: Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.
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.
authors.affiliation: Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Kocak
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Fatma Emel
authors.identifier: http://orcid.org/0000-0001-5549-3883
authors.initials: FE
authors.lastname: Kocak
authors.affiliation: Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Raziye
authors.initials: R
authors.lastname: Akcilar
authors.affiliation: Department of Biochemistry, Faculty of Art and Science, Dumlupinar University, Kutahya, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Bayat
authors.affiliation: Department of Urology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Bekir
authors.initials: B
authors.lastname: Aras
authors.affiliation: Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Mehmet Huseyin
authors.initials: MH
authors.lastname: Metineren
authors.affiliation: Department of Urology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yucel
authors.affiliation: Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Simsek
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000209:Acute-Phase Proteins; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D003401:Creatine / Q000097:blood; D019332:Endothelin-1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan; D014508:Urea / Q000097:blood
chemical_list: D000209:Acute-Phase Proteins; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D019332:Endothelin-1; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D009828:Oleanolic Acid; D014508:Urea; D001120:Arginine; D002216:Captopril; C445068:bardoxolone methyl; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D003401:Creatine; D000077333:Telmisartan
keywords: CDDO methyl ester; acute kidney injury; bardoxolone methyl; captopril; ischemia-reperfusion; kidney; telmisartan