Article

Effect of policosanol on carbon tetrachloride-induced acute liver damage in Sprague-Dawley rats.

Center of Natural Products from the National Center for Scientific Research, Havana City, Cuba.
Drugs in R & D (impact factor: 1.35). 01/2003; 4(1):29-35. pp.29-35
Source: PubMed

ABSTRACT Policosanol is a cholesterol-lowering drug purified from sugarcane (Saccharum officinarum, L.) wax. Beneficial pleiotropic effects of policosanol, such as inhibition of the susceptibility of low density lipoprotein to lipid peroxidation, have been shown. Policosanol has a good safety profile and well tolerated and, to date, no drug-related adverse effects have been demonstrated. Specifically, policosanol has not been shown to affect liver function or to increase liver enzyme levels in experimental or clinical studies.
This study was conducted to determine whether policosanol prevents liver damage induced by carbon tetrachloride (CCl4) in rats, since this model has been associated with an increased rate of lipid peroxidation.
Male Sprague-Dawley rats were randomised to four experimental groups: negative controls (no CCl4 or policosanol, group 1); positive controls (CCl4 but no policosanol, group 2); policosanol 25 mg/kg (group 3) and policosanol 100 mg/kg (group 4). Acute liver injury was induced in groups 2, 3 and 4 by CCl4 suspended in olive oil and administered at a dose of 1590 mg/kg via intraperitoneal injection. Eighteen hours after CCl4 dosing, the rats were anaesthetised and their livers removed for histopathological studies.
Policosanol 25 and 100 mg/kg dose dependently and significantly (p < 0.01) decreased the percentage of ballooned cells and hepatocytes with lipid inclusions and increased the percentage of normal hepatocytes compared with positive controls. The percentage inhibition of the occurrence of ballooned cells and hepatocytes with lipids was marked, reaching 71 and 49%, respectively, with the higher dose (100 mg/kg). The percentage of swollen hepatocytes was unchanged by policosanol compared with positive controls. No histological alterations in liver sections were found in the negative control group. Necrotic areas and inflammatory infiltrates were observed in the liver of seven of eight (87.5%) animals in the positive control group. However, only one of eight (12.5%) animals treated with policosanol 25 mg/kg and none (0%) treated with the higher dose (100 mg/kg) showed such a pattern.
Policosanol protected against the histological changes characteristic of CCl(4)-induced hepatic injury in rats, a model of hepatotoxicity in which the process of lipid peroxidation plays a role. Further studies aimed at demonstrating the connection between such hepatoprotective and antioxidant effects of policosanol must be initiated.

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    Article: Octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride.
    Yoshiji Ohta, Koji Ohashi, Tatsuya Matsura, Kenji Tokunaga, Akira Kitagawa, Kazuo Yamada
    [show abstract] [hide abstract]
    ABSTRACT: We examined whether octacosanol, the main component of policosanol, attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride (CCl(4)). In rats intoxicated with CCl(4) (1 ml/kg, i.p.), the activities of serum transaminases increased 6 h after intoxication and further increased at 24 h. In the liver of CCl(4)-intoxicated rats, increases in lipid peroxide (LPO) concentration and myeloperoxidase activity and decreases in superoxixde dismutase activity and reduced glutathione (GSH) concentration occurred 6 h after intoxication and these changes were enhanced with an increase in xanthine oxidase activity and a decrease in catalase activity at 24 h. Octacosanol (10, 50 or 100 mg/kg) administered orally to CCl(4)-intoxicated rats at 6 h after intoxication attenuated the increased activities of serum transaminases and the increased hepatic myeloperoxidase and xanthine oxidase activities and LPO concentration and the decreased hepatic superoxide dismutase and catalase activities and GSH concentration found at 24 h after intoxication dose-dependently. Octacosanol (50 or 100 mg/kg) administered to untreated rats decreased the hepatic LPO concentration and increased the hepatic GSH concentration. These results indicate that octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in CCl(4)-intoxicated rats.
    Journal of Clinical Biochemistry and Nutrition 04/2008; 42(2):118-25. · 1.98 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Beneficial pleiotropic effects
 
CCl4 dosing
 
cholesterol-lowering drug purified
 
clinical studies
 
drug-related adverse effects
 
experimental groups
 
group 2
 
group 4
 
groups 2
 
histological changes characteristic
 
inflammatory infiltrates
 
lipid inclusions
 
lipid peroxidation
 
liver damage induced
 
Male Sprague-Dawley rats
 
negative control group
 
negative controls
 
Policosanol 25
 
positive control group
 
positive controls