title: Pretreatment with mineralocorticoid receptor blocker reduces intestinal injury induced by ischemia and reperfusion: involvement of inhibition of inflammatory response, oxidative stress, nuclear factor κB, and inducible nitric oxide synthase.
abstract: BACKGROUND
  Spironolactone (Sp), a mineralocorticoid receptor antagonist, protects against the ischemia reperfusion (IR) injury of retina, kidney, heart, and brain. We aimed to investigate the effects of Sp on intestinal IR injury.
  
  
  METHODS
  Male Wistar rats were randomly divided into: (1) a sham control group; (2) an IR control group, subjected to 30 min ischemia and 3 h reperfusion; (3) a group treated with Sp (20 mg/kg) for 3 d before the IR; and (4) a sham-operated control group treated with Sp (20 mg/kg). After the reperfusion, blood and intestinal tissue samples were collected to evaluate histopathologic state, neutrophil infiltration (by measuring myeloperoxidase activity), levels of the cytokines (tumor necrosis factor α, interleukin 1α [IL-1α], interferon γ, monocyte chemotactic protein-1, granulocyte macrophage-colony stimulating factor, and IL-4), malondialdehyde (MDA) and reduced glutathione contents, and immunohistochemical expressions of nuclear factor κB, inducible nitric oxide synthase (iNOS), and caspase-3.
  
  
  RESULTS
  MDA content, myeloperoxidase activity, and plasma levels of tumor necrosis factor α, IL-1α, and monocyte chemotactic protein-1 were all elevated in IR, indicating the oxidative stress and local and systemic inflammatory response. Sp administration markedly reduced the MDA content and the cytokine levels. The pretreatment alleviated intestinal injury, neutrophil infiltration, and the expressions of caspase-3, iNOS, and NFκB.
  
  
  CONCLUSIONS
  The results implicate that Sp may have a strong protective effect against the intestinal IR injury. The effect can be mediated via suppression of both systemic inflammatory response and apoptosis through amelioration of oxidative stress and generation of proinflammatory cytokines, iNOS, caspase-3, and nuclear factor κB. Therefore, mineralocorticoid receptor antagonism might be of potential therapeutic benefit in cases of intestinal IR damage.
authors.affiliation: Department of Physiology, Bülent Ecevit University Medical School, Zonguldak, Turkey.
authors.forename: Hale Sayan
authors.initials: HS
authors.lastname: Ozacmak
authors.affiliation: Department of Physiology, Bülent Ecevit University Medical School, Zonguldak, Turkey. Electronic address: vhaktan@yahoo.com.
authors.forename: Veysel Haktan
authors.initials: VH
authors.lastname: Ozacmak
authors.affiliation: Department of Medical Pathology, Bülent Ecevit University Medical School, Zonguldak, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Barut
authors.affiliation: Department of Immunology, Bülent Ecevit University Medical School, Zonguldak, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Araslı
authors.affiliation: Department of General Surgery, Bülent Ecevit University Medical School, Zonguldak, Turkey.
authors.forename: Bulent Hamdi
authors.initials: BH
authors.lastname: Ucan
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D016328:NF-kappa B / Q000502:physiology*; D020556:Neutrophil Infiltration; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013148:Spironolactone / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione
keywords: Caspase-3; Cytokines; Intestinal ischemia reperfusion; Mineralocorticoid receptor blocker; NF-κB; Spironolactone; iNOS