Effect of simvastatin on mitochondrial enzyme activities, ghrelin, hypoxia-inducible factor 1 alpha in hepatic tissue during early phase of sepsis

Yorulmaz H., Ozkok E., ERGÜVEN M., Ates G., Aydin I., Tamer S.

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol.8, no.3, pp.3640-3650, 2015 (SCI-Expanded) identifier identifier


We aimed to investigate the effects of prior treatment of simvastatin on mitochondrial enzyme, ghrelin, and hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-alpha, IL-10 using ELISA. Liver sections underwent histopathologic examination and TNF-alpha, IL-10, HIF-1 alpha 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-alpha 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-1 alpha, 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-1 alpha levels.