Simvastatin maintains function and viability of steatotic rat livers procured for transplantation

KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins

“…Although a limitation of the experiment may be the use of cells from different animal sources, it certainly showed a global improvement in the sinusoidal microenvironment as the consequence of cells’ paracrine communications, thus validating the hypothesis that administration of simvastatin to individuals with sinusoidal microvascular injuries (ie, cirrhosis or ischaemia/reperfusion) exerts strong liver protection 46 47…”

Liver sinusoidal endothelial dysfunction after LPS administration: A role for inducible-nitric oxide synthase

“…In patients hospitalized for sepsis, not suffering from chronic liver disease, an early bilirubin increase at 48 h from admission is a marker of organ dysfunction and independently predicts survival [1]. Liver microcirculatory dysfunction has a strong impact on the viability of liver parenchymal and non-parenchymal cells [2], and this has been further emphasized by the demonstration of cytoprotective treatments improving liver microcirculation [3,27]. We have recently demonstrated that what occurs in conductance vessels and at the microcirculation of several organs, such as the heart, lung, brain and kidney [28] during endotoxemia endothelial dysfunction, also occurs at the hepatic microcirculation [3].…”

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

“…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].…”

“…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.…”

“…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.…”