title: Effect of simvastatin on mitochondrial enzyme activities, ghrelin, hypoxia-inducible factor 1α in hepatic tissue during early phase of sepsis.
abstract: We aimed to investigate the effects of prior treatment of simvastatin on mitochondrial enzyme, ghrelin, and hypoxia-inducible factor 1 α (HIF-1 α) on hepatic tissue in rats treated with Lipopolysaccharides (LPS) during the early phase of sepsis. Rats were divided into four groups: control, LPS (20 mg/kg, i.p.), Simvastatin (20 mg/kg, p.o.), and LPS + Simvastatin group. We measured citrate synthase, complex I, II, I-III, II-III enzymes activities, serum and tissue levels of TNF-α, IL-10 using ELISA. Liver sections underwent histopathologic examination and TNF-α, IL-10, HIF-1α and ghrelin immunoreactivity were examined using immunohistochemistry methods. There were no differences in all groups for mitochondrial enzyme activities. In terms of both ELISA and immunohistochemistry findings; the levels of serum and tissue TNF-α and IL-10 were higher in the experimental groups than controls (P < 0.05). In the LPS group, the hepatocyte cell membrane and sinusoid structure were damaged. In the Simvastatin +LPS group, hepatocytes and sinusoidal cord structure were partially improved. For HIF-1α, in all experimental groups immunoreactivity was increased (P < 0.05). In the Simvastatin group, Ghrelin levels were increased in comparison with the other groups (P < 0.01). Ghrelin levels were greatly decreased in LPS (P < 0.05). We observed that the degree of hepatocellular degeneration was partially reduced depending on the dosage and duration of prior simvastatin treatment with LPS, probably due to alterations of Ghrelin and HIF-1α levels.
authors.affiliation: Department of Physiology, Medical Faculty, Halic University Istanbul, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Yorulmaz
authors.affiliation: Department of Neuroscience, The Institue for Experimental Medicine, Istanbul University Istanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Ozkok
authors.affiliation: Faculty of Health Sciences, Istanbul Aydin University Istanbul, Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Erguven
authors.affiliation: Department of Basic Medical Sciences, Physiology, Istanbul Medical Faculty, Istanbul University Istanbul, Turkey.
authors.forename: Gulten
authors.initials: G
authors.lastname: Ates
authors.affiliation: Department of Basic Medical Sciences, Histology and Embriology, Istanbul Medical Faculty, Istanbul University Istanbul, Turkey.
authors.forename: Irfan
authors.initials: I
authors.lastname: Aydın
authors.affiliation: Department of Basic Medical Sciences, Physiology, Istanbul Medical Faculty, Istanbul University Istanbul, Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Tamer
keywords: Lipopolysaccharide; ghrelin; hypoxia-inducible factor 1-α; liver; mitochondrial enzyme activites; simvastatin