Effect of rosuvastatin on cholestasis‐induced hepatic injury in rat livers

Abstract

Recent studies reported that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have pleotropic effects independent of their lipid-lowering properties. The present study was undertaken to determine whether treatment with rosuvastatin (RO) would be beneficial in a rat model of bile duct ligation (BDL). Animals were divided into three groups: a sham group (group I), a BDL group treated with vehicle (group II), and a BDL group treated with RO (10 mg/kg) (group III). Serum levels of total bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase decreased significantly in group III when compared to group II. Lipid peroxides and NO levels of group III were found to be significantly lower than those of group II. Antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, and catalase) activity in liver tissues markedly decreased in group II, whereas treatment with RO preserved antioxidant enzyme activity. DT-diaphorase activity in group II was significantly higher than that in group III. The histopathological results showed multiple numbers of newly formed bile ductules with inflammatory cells infiltration in group II. These pathological changes were improved in group III. Our data indicate that RO ameliorates hepatic injury, inflammation, lipid peroxidation and increases antioxidant enzymes activity in rats subjected to BDL. RO may have a beneficial effect on treatment of cholestatic liver diseases.

Modification of hepatic iron metabolism induced by pravastatin during obstructive cholestasis in rats

“…The attenuation of cholestatic liver injury by statins has been demonstrated for several members of the group, and is currently ascribed to the ability of these agents to mitigate inflammatory and fibrotic responses in the liver (Awad and Kamel, 2010;Demirbilek et al, 2007;Dold et al, 2009;Trebicka et al, 2010). Our results in terms of improved morphological and biochemical responses, together with decreased α-SMA and PCNA levels, also confirm this mechanism for pravastatin for the first time, and provide the preclinical evidence for the formerly seen positive effect of pravastatin in patients with primary biliary cirrhosis (Kurihara et al, 1993).…”

“…In addition, pravastatin was administered to separate groups of cholestatic animals. The rationale was that statins -HMG-CoA reductase inhibitors -repeatedly demonstrated a protective anti-inflammatory and anti-oxidative influence during cholestatic liver injury (Awad and Kamel, 2010;Demirbilek et al, 2007;Dold et al, 2009;Trebicka et al, 2010). Part of this effect is ascribed to their ability to modulate heme oxygenase-1, the rate-limiting enzyme for heme degradation and free iron release (Muchova et al, 2007;Peterson et al, 2009).…”

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

“…but also have pleiotropic effects [13]. These drugs have been shown to reduce markers of liver injury in animal models of cholestasis [14–16]. Although these effects remain to be confirmed in clinical studies, statins seem to reduce bile acid production and increase cholesterol transport back to plasma; both regulated by nuclear receptors [17, 18].…”

Deteriorating effect of fluvastatin on the cholestatic liver injury induced by bile duct ligation in rats

“…Statins are widely used for lowering hypercholesterolemia, but increase in the evidence of their anti-inflammatory effects could extend the spectrum of their therapeutic usage. The sporadic studies have documented statins to reduce the development of cholestatic liver injury (Demirbilek et al 2007;Dold et al 2009;Awad and Kamel 2010). Contrary to these findings statins have a potential for adverse effects that could be mediated by induction of mitochondrial dysfunction (Velho et al 2006;Nadanaciva et al 2007;Hattori et al 2009;Lee et al 2010).…”