Fatma Emel Kocak1, Aysegul Kucuk2, Filiz Ozyigit3, Murat Tosun4, Cengiz Kocak5, Ahmet Kocak6, Mehmet Fatih Ekici7, Faik Yaylak8, Osman Genc2. 1. Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. Electronic address: dremelk@hotmail.com. 2. Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. 3. Department of Pharmacology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. 4. Department of Histology, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey. 5. Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. 6. Department of Histology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. 7. Department of General Surgery, Evliya Celebi Education and Research Hospital, Dumlupinar University, Kutahya, Turkey. 8. Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
Abstract
BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.
BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.
Authors: Jimme K Wiggers; Rowan F van Golen; Joanne Verheij; Annemiek M Dekker; Thomas M van Gulik; Michal Heger Journal: BMC Surg Date: 2017-04-11 Impact factor: 2.102
Authors: Carlos Henrique Marques Dos Santos; Doroty Mesquita Dourado; Baldomero Antonio Kato da Silva; Henrique Budib Dorsa Pontes; Euler de Azevedo Neto; Giovanna Serra da Cruz Vendas; Ian de Oliveira Chaves; João Victor Cunha Miranda; João Victor Durães Gomes Oliva; Letícia do Espírito Santo Dias; Murillo Henrique Martins de Almeida; Trícia Luna Sampaio Journal: Braz J Cardiovasc Surg Date: 2018 Mar-Apr
Authors: Carlos Henrique Marques Dos Santos; Doroty Mesquita Dourado; Baldomero Antonio Kato da Silva; Henrique Budib Dorsa Pontes; Euler de Azevedo-Neto; Giovanna Serra da Cruz Vendas; Ian de Oliveira Chaves; João Victor Cunha Miranda Journal: Arq Bras Cir Dig Date: 2017 Jul-Sep