title: Obestatin improves ischemia/reperfusion-induced renal injury in rats via its antioxidant and anti-apoptotic effects: role of the nitric oxide.
abstract: Obestatin was shown to have anti-inflammatory effects in several inflammatory models. To elucidate the potential renoprotective effects of obestatin, renal I/R injury was induced in male Sprague Dawley rats by placing a clamp across left renal artery for 60min following a right nephrectomy. Clamp was released and the rats were injected with either saline or obestatin (10, 30, 100μg/kg). In some experiments, obestatin (10μg/kg) was administered with L-NAME (10mg/kg) or L-Nil (0.36mg/kg). Following a 24-h reperfusion, the rats were decapitated to measure serum creatinine and nitrite/nitrate levels, renal malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity and to assess cortical necrosis and apoptosis scores. Obestatin treatment reduced I/R-induced increase in creatinine levels, renal MPO activity and renal MDA levels, while renal GSH levels were significantly increased by obestatin. Histological analysis revealed that severe I/R injury and high apoptosis score in the kidney samples of saline-treated rats were significantly reduced and the cortical/medullary injury was ameliorated by obestatin. Expression of eNOS, which was increased by I/R injury, was further increased by obestatin, while serum NO levels were significantly decreased. iNOS inhibitor L-Nil reduced oxidative renal damage and improved the functional and histopathological parameters. I/R-induced elevation in eNOS expression, which was further increased by obestatin, was depressed by L-NAME and L-Nil treatments. The present data demonstrate that obestatin ameliorates renal I/R-injury by its possible anti-oxidative, anti-inflammatory and anti-apoptotic properties, which appear to involve the suppression of neutrophil accumulation and modulation of NO metabolism.
authors.affiliation: Marmara University School of Medicine, Department of Internal Medicine, Division of Nephrology, Istanbul, Turkey; Marmara University School of Medicine, Department of Physiology, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Koç
authors.affiliation: Marmara University School of Medicine, Department of Physiology, Istanbul, Turkey.
authors.forename: Zarife Nigâr Özdemir
authors.initials: ZN
authors.lastname: Kumral
authors.affiliation: Marmara University School of Medicine, Department of Histology, Istanbul, Turkey.
authors.forename: Naziye
authors.initials: N
authors.lastname: Özkan
authors.affiliation: Kırklareli University Health School, Kırklareli, Turkey.
authors.forename: Gülsün
authors.initials: G
authors.lastname: Memi
authors.affiliation: Marmara University School of Medicine, Department of Biochemistry, Istanbul, Turkey.
authors.forename: Ömer
authors.initials: Ö
authors.lastname: Kaçar
authors.affiliation: Marmara University School of Medicine, Department of Biochemistry, Istanbul, Turkey.
authors.forename: Serpil
authors.initials: S
authors.lastname: Bilsel
authors.affiliation: Marmara University School of Medicine, Department of Histology, Istanbul, Turkey.
authors.forename: Şule
authors.initials: Ş
authors.lastname: Çetinel
authors.affiliation: Marmara University School of Medicine, Department of Physiology, Istanbul, Turkey. Electronic address: byegen@marmara.edu.tr.
authors.forename: Berrak Ç
authors.initials: BÇ
authors.lastname: Yeğen
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D054439:Ghrelin; D009569:Nitric Oxide
keywords: Nitric oxide; Obestatin; Oxidative stress; Renal ischemia-reperfusion injury