title: Beneficial pharmacological effects of levosimendan on antioxidant status of acute inflammation induced in paw of rat: involvement in inflammatory mediators.
abstract: Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. The purpose of this study was to examine anti-inflammatory effect and antioxidant activity of LEVO in a carrageenan (CAR)-induced inflammatory paw oedema rat model. The CAR-induced rat groups received LEVO 1, 2 and 3 mg/kg by intraperitonally and indomethacin (IND) 25 mg/kg by oral gavage. LEVO inhibited CAR-induced paw oedema and suppressed the production of TNF-α, IL-1 and IL-6 at doses of 2 and 3 mg/kg. In contrast to CAR-injected paws, 2 and 3 mg/kg doses of LEVO and IND increased superoxide dismutase (SOD) activity and also both doses of LEVO, and IND decreased the 8-isoprostaglandin F2α (8-ISO) level. A 2 mg/kg dose of LEVO produced 39%, 46%, 61% and 64.7% anti-inflammatory effects (p < 0.0001) for the 1st, 2nd, 3rd and 4th hours, respectively. Other results of our current study have shown that SOD and glutathione for CAR-injected groups were lower, and 8-ISO level was higher than those for the healthy rat group. LEVO may be provided as a pharmacological agent in the prevention or treatment of diseases in which acute or chronic inflammation occurs based on a pathogenic factor.
authors.affiliation: Department of Pharmacology and Toxicology, Ataturk University School of Veterinary, Erzurum, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.forename: Abdulmecit
authors.initials: A
authors.lastname: Albayrak
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.forename: Ali
authors.initials: A
authors.lastname: Aydin
authors.forename: Deniz
authors.initials: D
authors.lastname: Unal
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.forename: Irmak
authors.initials: I
authors.lastname: Ferah
authors.forename: Ersan
authors.initials: E
authors.lastname: Odaci
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan / Q000008:administration & dosage; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood; D035002:Lower Extremity; D008297:Male; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D006835:Hydrazones; D018836:Inflammation Mediators; D011724:Pyridazines; D000077464:Simendan; D002351:Carrageenan