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It has been reported that changes in cytokine levels affect mitochondrial functions, levels of hypoxia-inducible factor α (HIF-1α), and tissue damage during sepsis. We aimed to investigate the effects of simvastatin pretreatment on mitochondrial enzyme activities, and on levels of ghrelin, HIF-1α, and thiobarbituric acid reactive substances (TBARS) in kidney tissue during sepsis. Rats were separated into four groups, namely, control, lipopolysaccharides (LPS) (20 mg/kg), simvastatin (20 mg/kg), and simvastatin + LPS. We measured the levels of mitochondrial enzyme activities and TBARS in the kidney using spectrophotometry. The histological structure of the kidney sections was examined after staining with hematoxylin and eosin. Tumor necrosis factor α (TNF-α), IL-10, HIF-1α, and ghrelin immunoreactivity were examined using proper antibodies. In tissue, TNF-α (p < 0.01) and HIF-1α (p < 0.05) levels were increased in the simvastatin + LPS and LPS groups. TBARS levels were higher in the LPS group than in the other groups (p < 0.01), but they were similar in the simvastatin + LPS and control groups (p > 0.05). Ghrelin immunoreactivity was lower in the LPS group (p < 0.05) and higher in the simvastatin + LPS group than in the LPS group (p < 0.01). We observed tubular damage in the sections of the LPS group. There were no differences in mitochondrial enzyme activities between the groups (p > 0.05). We observed that pretreatment of simvastatin caused favorable changes on ghrelin and TBARS levels in rats with sepsis.
-
1.
Altunal C , Agalar F , Agalar C , Daphan C , Saygun O , Aydinuraz K , Sahiner T , Atasoy P , Caglayan O , Dom S : The effect of simvastatin on pulmonary damage in experimental peritonitis in rats. Indian J. Surg. 77(Suppl . 2), S370–S375 (2015)
-
2.
Ando H , Takamura T , Ota T , Nagai Y , Kobayashi K : Cerivastatin improves survival of mice with lipopolysaccharide-induced sepsis. J. Pharmacol. Exp. Ther. 294, 1043–1046 (2000)
-
3.
Andrades ME , Morina A , Spasić S , Spasojević I : Bench-to-bedside review: sepsis-from the redox point of view. Crit. Care 15(5), 230 (2011)
-
4.
Bertani T , Abbate M , Zoja C , Corna D , Perico N , Ghezzi P , Remuzzi G : Tumor necrosis factor induces glomerular damage in the rabbit. Am. J. Pathol. 134, 419–430 (1989)
-
5.
Buege JA , Aust SD : Microsomal lipid peroxidation methods. Methods Enzymol. 52, 302–310 (1978)
-
6.
Chvojka J , Sýkora R , Karvunidis T , Raděj J , Kroužecký A , Novák I , Matějovič M : New developments in septic acute kidney injury. Physiol. Res. 59, 859–869 (2010)
-
7.
Cunningham PN , Dyanov HM , Park P , Wang J , Newell KA , Quigg RJ : Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney. J. Immunol. 168, 5817–5823 (2002)
-
8.
Frede S , Stockmann C , Freitag P , Fandrey J : Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-κB. Biochem. J. 396, 517–527 (2006)
-
9.
Fukuzumi M , Shinomiya H , Shimizu Y , Ohishi Y , Utsumi S : Endotoxin-induced enhancement of glucose influx into murine peritoneal macrophages via GLUT1. Infect. Immun. 64, 108–112 (1996)
-
10.
Garrison RN , Ratcliffe DJ , Fry DE : The effects of peritonitis on murine renal mitochondria. Adv. Shock Res. 7, 71–76 (1982)
-
11.
Geller ER , Jankauskas S , Kirkpatrick J : Mitochondrial death in sepsis: a failed concept. J. Surg. Res. 40, 514–517 (1986)
-
12.
Hataya Y , Akamizu T , Hosoda H , Kanamoto N , Moriyama K , Kangawa K , Takaya K , Nakao K : Alterations of plasma ghrelin levels in rats with lipopolysaccharide-induced wasting syndrome and effects of ghrelin treatment on the syndrome. Endocrinology 144, 5365–5371 (2003)
-
13.
Inoue T , Saito H , Fukushima R , Inaba T , Lin MT , Fukatsu K , Muto T : Growth hormone and insulin like growth factor I enhance host defense in a murine sepsis model. Arch. Surg. 130, 1115–1122 (1995)
-
14.
Işeri S , Ercan F , Gedik N , Yüksel M , Alican I : Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology 230(2 – 3), 256–264 (2007)
-
15.
Jaber BL : The cytokine network in acute renal failure. Nephrol. Rounds 3, 31–36 (2005)
-
16.
Jeger V , Djafarzadeh S , Jakob SM , Takala J : Mitochondrial function in sepsis. Eur. J. Clin. Invest. 43, 532–542 (2013)
-
17.
Kim HY , Kim YH , Nam BH , Kong HJ , Kim HH , Kim YJ , An WG , Cheong J : HIF-1α expression in response to lipopolysaccaride mediates induction of hepatic inflammatory cytokine TNFα. Exp. Cell Res. 313, 1866–1876 (2007)
-
18.
King TE , Howard RL : Preparation and properties of soluble NADH dehydrogenase from cardiac muscle. Methods Enzymol. 10, 275–294 (1967)
-
19.
Liao W , Rudling M , Angelin B : Contrasting effects of growth hormone and insulin-like growth factor I on the biological activities of endotoxin in the rat. Endocrinology 138, 289–295 (1997)
-
20.
Mason KE , Stofan DA : Endotoxin challenge reduces aconitase activity in myocardial tissue. Arch. Biochem. Biophys. 469, 151–156 (2008)
-
21.
McGivney A , Bradley SG : Action of bacterial endotoxin and lipid A on mitochondrial enzyme activities of cells in culture and subcellular fractions. Infect. Immun. 25, 664–671 (1979)
-
22.
McGuigan PJ , O’Kane CM , McAuley DF : Benefits of statins in the critically ill: promising but not proven. Crit. Care Med. 39, 1599–1600 (2011)
-
23.
Ota T , Ota K , Jono H , Fujimori H , Ueda M , Shinriki S , Sueyoshi T , Shinohara M , Ando Y : Midkine expression in malignant salivary gland tumors and its role in tumor angiogenesis. Oral Oncol. 46, 657–661 (2010)
-
24.
Ozkok E , Yorulmaz H , Ates G , Serdaroglu-Oflazer P , Tamer AS : Effects of prior treatment with simvastatin on skeletal muscle structure and mitochondrial enzyme activities during early phases of sepsis. Int. J. Clin. Exp. Pathol. 7, 8356–8365 (2014)
-
25.
Panichi V , Paoletti S , Mantuano E , Manca-Rizza G , Filippi C , Santi S , Taccola D , Donadio C , Tramonti G , Innocenti M , Casto G, Consani C, Sbragia G, Franzoni F, Galetta F, Panicucci E, Barsotti G: In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients. Nephrol. Dial. Transplant. 21, 337–344 (2006)
-
26.
Peyssonnaux C , Cejudo-Martin P , Doedens A , Zinkernagel AS , Johnson RS , Nizet V : Cutting edge: essential role of hypoxia inducible factor-1α in development of lipopolysaccharide-induced sepsis. J. Immunol. 178, 7516–7519 (2007)
-
27.
Poole S , Bird TA , Selkirk S , Gaines-Das RE , Choudry Y , Stephenson SL , Kenny AJ , Saklatvaa J : Fate of injected interleukin1 in rats: sequestration and degradation in the kidney. Cytokine 2, 416–422 (1990)
-
28.
Porta F , Takala J , Weikert C , Bracht H , Kolarova A , Lauterburg BH , Borotto E , Jakob SM : Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function. Crit. Care 10, R118 (2006)
-
29.
Russo MW , Scobey M , Bonkovsky HL : Drug-induced liver injury associated with statins. Semin. Liver Dis. 29, 412–422 (2009)
-
30.
Santos Fdo N , Watanabe M , Vasco CF , Fonseca CD , Vattimo Mde F : Antioxidant protection of statins in acute kidney injury induced by sepsis. Rev. Esc. Enferm. USP 48(5), 820–826 (2014)
-
31.
Scottocosa GL , Kuylenstierna B , Ernster L , Bergstrand A : An electron transport system associated with the outer membrane of the mitochondria. J. Cell Biol. 32, 415–438 (1967)
-
32.
Singer M , Brealey D : Mitochondrial dysfunction in sepsis. Biochem. Soc. Symp. 66, 149–166 (1999)
-
33.
Slotta JE , Laschke MW , Schilling MK , Menger MD , Jeppsson B , Thorlacius H : Simvastatin attenuates hepatic sensitization to lipopolysaccharide after partial hepatectomy. J. Surg. Res. 162, 184–192 (2010)
-
34.
Teshima CAS , Dezoti C , Watanabe M , Vattimo MFF : A estatina e a lesão renal aguda isquêmica em ratos [Statin and acute ischemic renal injury in rats]. Acta Paul. Enferm. 25(1), 86–89 (2012)
-
35.
Viasus D , Garcia-Vidal C , Simonetti AF , Dorca J , Llopis F , Mestre M , Morandeira-Rego F , Carratalà J : The effect of simvastatin on inflammatory cytokines in community acquired pneumonia: a randomised, double-blind, placebo-controlled trial. BMJ Open 5, e006251 (2015)
-
36.
Wu R , Dong W , Cui X , Zhou M , Simms HH , Ravikumar TS , Wang P : Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve. Ann. Surg. 245, 480–486 (2007)
-
37.
Xu C , Chang A , Hack BK , Eadon MT , Alper SL , Cunningham PN : TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis. Kidney Int. 85, 72–81 (2014)
-
38.
Yasuda H , Yuen PST , Hu X , Zhou H , Star RA : Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects. Kidney Int. 69, 1535–1542 (2006)
-
39.
Yorulmaz H , Ozkok E , Erguven M , Ates G , Aydın I , Tamer S : Effect of simvastatin on mitochondrial enzyme activities, ghrelin, hypoxia-inducible factor 1α in hepatic tissue during early phase of sepsis. Int. J. Clin. Exp. Med. 8, 3640–3650 (2015)
-
40.
Young L (1995): Sepsis syndrome. In: Principles and Practice of Infectious Diseases, eds Mandel G, Bennet J, Dolin R, Churchill Livingston, New York, pp. 690–705
-
41.
Zarjou A , Agarwal A : Sepsis and acute kidney injury. J. Am. Soc. Nephrol. 22, 999–1006 (2011)
-
42.
Zinkernagel AS , Johnson RS , Nizet U : Hypoxia inducible factor (HIF) function in innate immunity and infection. J. Mol. Med. (Berl.) 85, 1339–1346 (2007)
Editor-in-Chief
László ROSIVALL (Semmelweis University, Budapest, Hungary)
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Anna BERHIDI (Semmelweis University, Budapest, Hungary)
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- Magdolna DANK (Semmelweis University, Budapest, Hungary)
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- Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
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