title: The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress.
abstract: Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. Amiodarone is a class III antiarrhythmic agent, a multichannel blocker (Ca++, Na+, and K+), and a noncompetitive α- and β-adrenergic blocker in cardiac cells. The present study aimed to determine whether amiodarone was protective against experimentally induced cecal ligation and puncture sepsis in rat lung tissue. The relationship between its probable protective effect and antioxidant/anticytokine action biochemically and histopathologically was also examined. Five groups of rats were used, each composed of 20 rats: (1) the sham-operated control group; (2) the CLP group; (3) the 25-mg/kg amiodarone-treated control healthy group; (4) the 50-mg/kg amiodarone-treated CLP group; and (5) the 50-mg/kg amiodarone-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All groups were sacrificed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. Twenty-five and 50 mg/kg amiodarone decreased the level of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in serum and 8-iso-prostaglandin F2α level in lung tissue. They increased the activities of superoxide dismutase and levels of total glutathione in lung tissues of rats. Histopathological scores and examinations were in accordance with the biochemical results. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups. The CLP + amiodarone 50 mg/kg group had the lowest inflammation score among CLP groups. Our results indicate that administration of amiodarone prevented oxidative stress and cytokine action and protected lung tissue during sepsis cascade.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.forename: Deniz
authors.initials: D
authors.lastname: Unal
authors.forename: Bulent Caglar
authors.initials: BC
authors.lastname: Bilgin
authors.forename: Tugba Nurcan
authors.initials: TN
authors.lastname: Yuksel
authors.forename: Serhat
authors.initials: S
authors.lastname: Vancelik
mesh_terms: D000638:Amiodarone / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002432:Cecum; D016207:Cytokines / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008026:Ligation; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016207:Cytokines; D020011:Protective Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D013482:Superoxide Dismutase; D005978:Glutathione; D000638:Amiodarone