Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model

Koçak, Fatma Emel; Küçük, Ayşegül; Özyiğit, Filiz; Tosun, Murat; Koçak, Cengiz; Koçak, Ahmet; Ekici, Mehmet Fati̇h; Yaylak, Faik; Genç, Osman

doi:10.1016/j.jss.2015.06.009

Cited by 15 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the previous studies about I/R injury, 1.5-to 4-fold of basal level of MDA was obtained 9,[22][23][24] . Therefore, it is certain that the tissue MDA level can reflect exactly the severity of the oxidative stress injury.…”

Section: Results Of Histopathological Analysismentioning

confidence: 99%

Grape seed protects cholestatic rats liver from ischemia/reperfusion injury

et al. 2016

View full text Add to dashboard Cite

PURPOSE:To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS:Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed.RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION:Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.

show abstract

Section: Results Of Histopathological Analysismentioning

confidence: 99%

Grape seed protects cholestatic rats liver from ischemia/reperfusion injury

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Atorvastatin has been shown to protect against I/R injury in experimental models of normal and steatotic livers [20, 21, 27, 28]. Even short-term therapy with ATV (5 mg/kg) just 1 h before ischemia in normal and steatotic mouse livers conferred a 70–90% reduction in post-I/R necrosis [23].…”

Section: Discussionmentioning

confidence: 99%

“…Even short-term therapy with ATV (5 mg/kg) just 1 h before ischemia in normal and steatotic mouse livers conferred a 70–90% reduction in post-I/R necrosis [23]. Other studies used varying dosages of statin pretreatment at varying time points and found similar effects in reduction of hepatopathology; these regimens included ATV pretreatment 10 mg/kg 24 h and again 1 h before ischemia induction, [33] Simvastatin (5 mg/kg) pretreatment 1 h before ischemia induction, [28] and Simvastatin (1 mg/kg) even 30 min before ischemia induction [21]. Key mechanisms include suppression of inflammation and microvascular protection.…”

Section: Discussionmentioning

confidence: 99%

“…Statins also upregulate endothelial nitric oxide synthase (eNOS) production [21, 24]. eNOS stimulates the production and bioavailability of nitric oxide (NO) in the vascular endothelium, which subsequently causes vasodilatation of the hepatic microvasculature, and suppresses thromboxane A2 production [25, 28]. Another study found that vasoprotective effects of ATV were modulated through a decrease in intracellular adhesion molecule-1 (ICAM-1) and preservation of antithrombin-III (ATIII) levels [33].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, statins have previously been reported to protect against I/R injury in normal and steatotic mouse livers. The supposed underlying mechanisms of statin protection include antioxidant, [19], vasoprotective, [20–25] anti-inflammatory, [20, 26] and anti-thrombotic effects [20, 21, 27, 28]. In that respect, the dual hepatoprotective properties of statins, as outlined in Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Atorvastatin does not protect against ischemia-reperfusion damage in cholestatic rat livers

et al. 2017

View full text Add to dashboard Cite

BackgroundExtrahepatic cholestasis sensitizes the liver to ischemia/reperfusion (I/R) injury during surgery for perihilar cholangiocarcinoma. It is associated with pre-existent sterile inflammation, microvascular perfusion defects, and impaired energy status. Statins have been shown to protect against I/R injury in normal and steatotic mouse livers. Therefore, the hepatoprotective properties of atorvastatin were evaluated in a rat model of cholestatic I/R injury.MethodsMale Wistar rats were subjected to 70% hepatic ischemia (during 30 min) at 7 days after bile duct ligation. Rats were randomized to atorvastatin treatment or vehicle-control in three test arms: (1) oral treatment with 5 mg/kg during 7 days after bile duct ligation; (2) intravenous treatment with 2.5, 5, or 7.5 mg/kg at 24 h before ischemia; and (3) intravenous treatment with 5 mg/kg at 30 min before ischemia. Hepatocellular damage was assessed by plasma alanine aminotransferase (ALT) and histological necrosis.ResultsI/R induced severe hepatocellular injury in the cholestatic rat livers (~10-fold increase in ALT at 6 h after I/R and ~30% necrotic areas at 24 h after I/R). Both oral and intravenous atorvastatin treatment decreased ALT levels before ischemia. Intravenous atorvastatin treatment at 5 mg/kg at 24 h before ischemia was the only regimen that reduced ALT levels at 6 h after reperfusion, but not at 24 h after reperfusion. None of the tested regimens were able to reduce histological necrosis at 24 h after reperfusion.ConclusionPre-treatment with atorvastatin did not protect cholestatic livers from hepatocellular damage after I/R. Clinical studies investigating the role of statins in the protection against hepatic I/R injury should not include cholestatic patients with perihilar cholangiocarcinoma. These patients require (pharmacological) interventions that specifically target the cholestasis-associated hepatopathology.

show abstract