title: Protective effects of lithium: a new look at an old drug with potential antioxidative and anti-inflammatory effects in an animal model of sepsis.
abstract: Sepsis is the systemic response of an organism against microorganisms and toxins. Lithium is a therapeutic agent used for bipolar disorder and neurodegenerative disease, and it exerts pleiotropic effects on various cellular processes. The present study aimed to determine the effect of lithium on cecal ligation and puncture (CLP)-induced tissue injury in the lungs, by inhibiting the pro-inflammatory cytokine response, and the generation of reactive oxygen species (ROS) triggered by polymicrobial sepsis. Five groups of 20 rats each were used: 1) sham-operated control group; 2) CLP group; 3) 50mg/kg lithium-treated control healthy group; 4) 25 mg/kg lithium-treated CLP group; and 5) 50 mg/kg lithium-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All rat groups were killed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. The 25 and 50 mg/kg of lithium decreased the level of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and the tumor necrosis factor-α (TNF-α) in the serum, and the 8-iso-prostaglandin F2α (8-ISO) level in lung tissue. The lithium also increased the activity of superoxide dismutase (SOD) and the total levels of glutathione (GSH) in the lung tissues of rats. The histopathological scores and examinations were in accordance with the biochemical results, and revealed significant differences in the inflammation scores between the sepsis group and the other groups. The CLP+lithium 50mg/kg group had the lowest inflammation score among the CLP groups. Our results indicated that the therapeutic administration of lithium prevented oxidative stress changes and cytokine changes, and also protected vital tissues.
authors.affiliation: Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey. dramecit@atauni.edu.tr
authors.forename: Abdulmecit
authors.initials: A
authors.lastname: Albayrak
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.forename: Semih
authors.initials: S
authors.lastname: Kunak
authors.forename: Saliha Sena
authors.initials: SS
authors.lastname: Karcioglu
authors.forename: Serdar
authors.initials: S
authors.lastname: Yigit
authors.forename: Deniz
authors.initials: D
authors.lastname: Unal
authors.forename: Sabri Selcuk
authors.initials: SS
authors.lastname: Atamanalp
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D016651:Lithium Carbonate / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; C075750:8-epi-prostaglandin F2alpha; D016651:Lithium Carbonate; D015237:Dinoprost; D013482:Superoxide Dismutase; D005978:Glutathione