Acute Liver Damage In Rats Research Articles

Single dose intravenous thioacetamide administration as a model of acute liver damage in rats

Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-alpha and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage.

EFFECT OF GARLIC ON HEMOSTASIS IN HYPERLIPIDEMIA

The fruits of Aronia melanocarpa are rich in anthocyanins — plant pigments with anti-inflammatory and anti-oxidant activity. We studied the effect of the natural fruit juice from A. melanocarpa (NFJAM) on carbon tetrachloride (CCl4)-induced acute liver damage in rats. Histopathological changes such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins occurred in rats following acute exposure to CCl4 (0.2 ml kg−1, 2 days). The administration of CCl4 increased plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, induced lipid peroxidation (as measured by malondialdehyde (MDA) content in rat liver and plasma) and caused a depletion of liver reduced glutathione (GSH). NFJAM (5, 10 and 20 ml kg−1, 4 days) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities, induced by CCl4 (0.2 ml kg−1, 3rd and 4th days). NFJAM also prevented the CCl4-induced elevation of MDA formation and depletion of GSH content in rat liver.

Duration-dependent hepatoprotective effects of propolis extract against carbon tetrachloride-induced acute liver damage in rats

Propolis is a natural product produced by bees that was discovered through the study of traditional cures and knowledge of indigenous people throughout the world. It is rich in vitamins A, B, C, and E, and in amino acids, copper, iron, manganese, and zinc. The investigators studied the duration-dependent hepatoprotective effects of propolis extract (200 mg/kg, orally) against carbon tetrachloride (CCl 4; 1.5 mL/kg, intraperitoneally)-induced liver damage in rats. Administration of CCl 4 caused a sharp elevation in the activity of serum transaminases and serum alkaline phosphatase. A significant depletion in hepatically reduced glutathione was observed with significantly enhanced hepatic lipid peroxidation. After CCl 4 administration, glycogen contents and activities of alkaline phosphatase, adenosine triphosphatase, and succinic dehydrogenase were significantly decreased, whereas total protein contents and activity of acid phosphatase were increased in the liver and kidney. Propolis extract reversed alterations in all parameters when administered within 6, 12, and 24 h of toxicant exposure. Propolis therapy produced duration-dependent protection, with maximal protection achieved at 24 h after CCl 4 exposure. It is believed that propolis in its natural form has general pharmacologic value and marked hepatoprotective potential because of its composition of minerals, flavonoids, and phenolic compounds.

Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride-induced acute liver damage in rats

The hepatoprotective effect of ethanolic extract and its four different fractions (CHCl 3, EtOAc, n-BuOH, and remaining water fraction) of Vitis vinifera L. leaves was investigated against carbon tetrachloride (CCl 4)-induced acute hepatotoxicity in rats. The ethanolic extract was found active at 125 mg/kg dose (per os). The ethanolic extract was fractionated through successive solvent–solvent extractions and the n-BuOH fraction in 83 mg/kg dose possessed remarkable antioxidant and hepatoprotective activities. Liver damage was assessed by using biochemical parameters (plasma and liver tissue MDA [malondialdehyde], transaminase enzyme levels in plasma [AST-aspartate transaminase, ALT-alanine transferase] and liver GSH [glutathione] levels). Additionally, the pathological changes in liver were evaluated by histopathological studies. Legalon 70 ® Protect was used as standard natural originated drug.

Curcumin–phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats

A novel formulation of curcumin in combination with the phospholipids was developed to overcome the limitation of absorption and to investigate the protective effect of curcumin–phospholipid complex on carbon tetrachloride induced acute liver damage in rats. The antioxidant activity of curcumin–phospholipid complex (equivalent of curcumin 100 and 200 mg/kg body weight) and free curcumin (100 and 200 mg/kg body weight) was evaluated by measuring various enzymes in oxidative stress condition. Curcumin–phospholipid complex significantly protected the liver by restoring the enzyme levels of liver glutathione system and that of superoxide dismutase, catalase and thiobarbituric acid reactive substances with respect to carbon tetrachloride treated group ( P < 0.05 and <0.01). The complex provided better protection to rat liver than free curcumin at same doses. Serum concentration of curcumin obtained from the complex (equivalent to 1.0 g/kg of curcumin) was higher ( C max 1.2 μg/ml) than pure curcumin (1.0 g/kg) ( C max 0.5 μg/ml) and the complex maintained effective concentration of curcumin for a longer period of time in rat serum. The result proved that curcumin–phospholipid complex has better hepatoprotective activity, owe to its superior antioxidant property, than free curcumin at the same dose level.

Hepatoprotective effect of the natural fruit juice from Aronia melanocarpa on carbon tetrachloride-induced acute liver damage in rats

The fruits of Aronia melanocarpa are rich in anthocyanins — plant pigments with anti-inflammatory and anti-oxidant activity. We studied the effect of the natural fruit juice from A. melanocarpa (NFJAM) on carbon tetrachloride (CCl 4)-induced acute liver damage in rats. Histopathological changes such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins occurred in rats following acute exposure to CCl 4 (0.2 ml kg −1, 2 days). The administration of CCl 4 increased plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, induced lipid peroxidation (as measured by malondialdehyde (MDA) content in rat liver and plasma) and caused a depletion of liver reduced glutathione (GSH). NFJAM (5, 10 and 20 ml kg −1, 4 days) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities, induced by CCl 4 (0.2 ml kg −1, 3rd and 4th days). NFJAM also prevented the CCl 4-induced elevation of MDA formation and depletion of GSH content in rat liver.

Evaluation of the protective efficacy of Asteracantha longifolia on acetaminophen-induced liver damage in rats.

The effect of oral administration of methanolic extract of Asteracantha longifolia (AL) seeds on acetaminophen (APAP)-induced acute liver damage in rats was investigated. The activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transferase) and bilirubin level in serum and the levels of cholesterol, triglycerides, and free fatty acids in both serum and liver were found to be increased when rats were challenged with APAP. This was also associated with a significant reduction of serum and tissue phospholipids. Pretreatment with AL extract prior to the administration of APAP prevented these alterations as evidenced by liver histopathology. Results indicated that the extract could offer protection against APAP-induced liver damage, suggesting its hepatoprotective activity.

Protective effect of carnosol on CCl(4)-induced acute liver damage in rats.

We recently reported that (Lamiaceae) may alleviate CCl(4)-induced acute hepatotoxicity in rats, possibly blocking the formation of free radicals generated during CCl(4) metabolism. Carnosol, one of the main constituents of Rosmarinus, has been shown to have antioxidant and scavenging activities. Therefore, it is plausible to expect that carnosol may mediate some of the effects of Rosmarinus on oxidative stress consequences induced by CCl(4) in the liver. We evaluated the effectiveness of carnosol to normalize biochemical and histological parameters of CCl(4)-induced acute liver injury. Male Sprague Dawley rats (n = 5) injured by CCl(4) (oral dose 4 g/kg of body weight) were treated with a single intraperitoneal dose (5 mg/kg) of carnosol. Twenty-four hours later, the rats were anaesthetized deeply to obtain the liver and blood, and biochemical and histological parameters of liver injury were evaluated. Carnosol normalized bilirubin plasma levels, reduced malondialdehyde (MDA) content in the liver by 69%, reduced alanine aminotransferase (ALT) activity in plasma by 50%, and partially prevented the fall of liver glycogen content and distortion of the liver parenchyma. Carnosol prevents acute liver damage, possibly by improving the structural integrity of the hepatocytes. To achieve this, carnosol could scavenge free radicals induced by CCl(4), consequently avoiding the propagation of lipid peroxides. It is suggested that at least some of the beneficial properties of Rosmarinus officinalis are due to carnosol.

The effectiveness of Tsu-San-Li (St-36) and Tai-Chung (Li-3) acupoints for treatment of acute liver damage in rats.

This study investigated the effects of acupuncture on carbon tetrachloride (CCl4) induced acute liver injury in male rats (n=36). The experimental groups were injected with CCl4 before, during, or after acupuncture therapy. Acupoints similar to the human Tsu-San-Li (St-36) and Tai-Chung (Li-3) were needled bilaterally. Rats treated with CCl4 had higher levels of serum glutamate-oxalate-transaminase (sGOT) and serum glutamate-pyruvate-transaminase (sGPT). Comparing the experimental groups, biochemical and pathological parameters of liver injury were significantly reduced when rats were acupunctured after, not before, CCl4-induced hepatotoxicity. Acupuncture at the Tsu-San-Li and Tai-Chung acupoints cannot prevent acute liver injury but may be effective in treating liver injury induced by carbon tetrachloride in rats.

Protective effect of low dose lipopolysaccharide-induced hepatic endogenous nitric oxide and nitric oxide donors in acetaminophen-induced acute liver damage in rats

Protective effect of low dose lipopolysaccharide-induced hepatic endogenous nitric oxide and nitric oxide donors in acetaminophen-induced acute liver damage in rats

The evaluation of the therapeutic effect of tao-shang-tsao on alpha-naphthylisothiocyanate and carbon tetrachloride-induced acute liver damage in rats.

The hepatoprotective effects of Tao-shang-tsao, Ixeris laevigata Sch.-Bip. var. oldhami Kitam., were studied on cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT, 100 mg/10 ml/kg, in olive oil, i.p.) and acute hepatitis induced by carbon tetrachloride (20% CCl4/olive oil, 1.5 ml/kg, i.p.) in rats by post-treatment with the crude methanolic extracts of I. laevigata (0.3, 1.0, and 2.0 g/kg) orally in the therapeutic model. Hepatoprotective activity was monitored by estimating the serum transaminases concentrations and histopathological changes in the livers of experimental rats. It was found that the I. laevigata extract significantly decreased the acute elevation of serum transaminases by biochemical examination. According to pathohistological studies in the liver of experimental rats, the crude I. laevigata extract ameliorates the central necrosis, fatty change or proliferation of bile duct epithelium focal necrosis caused by ANIT or CCl4-induced hepatitis rats.

Evaluation of four prescriptions of traditional Chinese medicine: Syh-Mo-Yiin, Guizhi-Fuling-Wan, Shieh-Qing-Wan and Syh-Nih-Sann on experimental acute liver damage in rats

Syh-Mo-Yiin (SMY), Guizhi-Fuling-Wan (GFW), Shieh-Qing-Wan (SQW) and Syh-Nih-Sann (SNS) are four prescriptions of Traditional Chinese Medicine (TCM) used in the remedy of liver trouble in various types. The hepatoprotective effects of water extracts of these four recipes against d-galactosamine ( d-GalN) and carbon tetrachloride (CCl 4)-induced acute hepatic damage were determined in rats. The results indicated that the serum glutamate-oxalate-transaminase (sGOT) and the serum glutamate-pyruvate-transaminase (sGPT) levels provoked by d-GalN and CCl 4 decreased after treatment with these prescriptions of TCM. Histological changes around portal area ( d-GalN-induced hepatotoxicity) and central vein (CCl 4-induced hepatotoxicity) were simultaneously improved by the treatment with TCM mentioned above.

Inhibitory effects of prostaglandin E1.alpha-cyclodextrin (PGE1.CD) on dimethylnitrosamine-induced acute liver damage in rats

The effects of PGE1.CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1.CD was administered i.v. from 30 min before to 24 hr after DMN-intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1.CD (0.2-2 micrograms/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HPT, GOT, GPT, LDH, LAP, T-Bil) caused by DMN-intoxication. PGE1.CD (0.5 microgram/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1.CD (2 micrograms/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1.CD (2 micrograms/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1.CD (1 microgram/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1.CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid.