DEVELOPMENT OF CARBON TETRACHLORIDE-INDUCED CHRONIC HEPATOTOXICITY MODEL IN RATS AND ITS APPLICATION IN EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF SILYMARIN

Objective: The objective of the present work is to develop carbon tetrachloride (CCl4)-induced chronic hepatotoxicity model in rats and its applicationin evaluation of hepatoprotective activity of silymarin.Methods: Animals were divided into four groups. Three groups were the disease induction group and 4th was the treatment group. In disease inductiongroups, chronic liver injury was induced by administration of CCl4 through intraperitoneal route (1 ml/kg) for 7-8 weeks. For treatment Group, 1 mlsilymarin suspension (orally) and CCl4 was given for 7-8 weeks. During disease induction and treatment period (7-8 weeks), blood samples werecollected and serum was separated which in turn used to analyze liver function tests such as serum glutamate oxaloacetate transaminase (SGOT),serum glutamate pyruvate transaminase (SGPT), alkaline phosphate (ALP), direct bilirubin, total protein (TP), and albumin (Alb) levels. Along withliver functional tests, tests to check cholesterol, glucose, and malondialdehyde (MDA) were also performed. Liver fibrosis and cirrhosis was quantifiedby histopathological studies of small portion of the excised liver. Model was validated by repetition of the experiment. Intermediate dissection wascarried out to measure an extent of liver damage.Result: Serum SGOT, SGPT, ALP, and direct bilirubin were found to be significantly higher in CCl4 intoxicated rats. TP and Alb were decreased, andMDA was found to be significantly higher in CCl4 intoxicated rats, which is the main end product of lipid peroxidation. Whereas in the treatment groupsilymarin improved the liver functions in CCl4 toxicated drug.Conclusion: We conclude that protein oxidation may play a role in the pathogenesis of CCl4 induced liver injury. The accumulation of oxidized proteinsmay be an early indication of CCl4 induced liver damage and silymarin found to be effective in liver injury by inhibiting protein oxidation.

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Development of Hepatotoxicity Model in Rats and its Application in Evaluation of Hepatoprotective Activity of Cell Wall Contents of Probiotics

INTERNATIONAL JOURNAL OF TOXICOLOGICAL AND PHARMACOLOGICAL RESEARCH ◽

10.25258/ijtpr.v9i03.9072 ◽

2017 ◽

Vol 9 (03) ◽

Author(s):

Shah G. H. ◽

Patel B. G. ◽

Shah G. B.

Keyword(s):

Cell Wall ◽

Liver Injury ◽

Protein Oxidation ◽

Total Protein ◽

Treated Group ◽

Saline Group ◽

Hepatoprotective Activity ◽

Direct Bilirubin ◽

Control Group ◽

Standard Drug

The objective of present work is Development of Hepatotoxicity model in rats and to evaluate hepatoprotective activity of cell wall contents of probiotics. Animals were divided in four groups. The groups were normal saline group, diseased control group, standard drug treated group and 4th group was CCl4 +Cell wall contents of probiotics. In diseased control group chronic liver injury was induced by administration of Carbontetrachloride (CCl4) via intraperitoneal route (1 ml/kg) for seventy days. For standard drug treated group 1 ml Silymarin suspension (Orally) and CCl4 was given for seventy days. In fourth group cell wall contents (1 x 10 12 CFU/ml/animal) and CCl4 was given for seventy days. During disease induction and treatment period blood samples were collected and serum was separated which was used to analyse various parameters like Alanine aminotransferase (ALT), Aspartate aminotransferase, (AST), Alkaline phosphate (ALP), direct bilirubin, total protein and albumin levels to asses liver function. Along with these cholesterol, Glucose and Malondialdehyde were also measured. Liver fibrosis and cirrhosis was quantified by histopathological studies of small portion of the excised liver. Serum AST, ALT, ALP, and direct bilirubin were found to be significantly higher in CCl4 intoxicated rats. Total protein and albumin was decreased. Manondialdehyde was found to be significantly higher in CCl4 intoxicated rats which was main end product of Lipid Peroxidation. Whereas in cell wall contents probiotics and silymarin treated group improve the liver functions in CCl4 toxicated rats. We conclude that protein oxidation may play a role in the pathogenesis of CCl4 induced liver injury and that the accumulation of oxidised proteins may be an early indication of CCl4 induced liver damage. Silymarin and cell wall contents of probiotics were effective in liver injury by inhibiting protein oxidation.

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Hepatoprotective activity of Adina cordifolia against ethanol induce hepatotoxicity in rats

International Current Pharmaceutical Journal ◽

10.3329/icpj.v1i9.11619 ◽

2012 ◽

Vol 1 (9) ◽

pp. 279-284 ◽

Cited By ~ 5

Author(s):

A Sharma ◽

B Sangameswaran ◽

V Jain ◽

M S Saluja

Keyword(s):

Pharmaceutical Journal ◽

Hepatoprotective Activity ◽

Serum Markers ◽

Hepatocellular Injury ◽

Standard Drug ◽

Blood Samples ◽

Hepatic Cells ◽

Serum Glutamate Pyruvate Transaminase ◽

Histopathological Studies ◽

Serum Glutamate

The acetone (AEAC) and aqueous extracts (AQEAC) of Adina cordifolia, belonging to the family Rubiaceae, were studied for hepatoprotective activity against Wister rats with liver damage induced by ethanol. It was found that AEAC and AQEAC, at a dose of 500 mg/kg body weight exhibited hepatoprotective effect by lowering the Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), alkaline phosphate and total bilirubin to a significant extent and also significantly increased the levels of total protein. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Since results of biochemical studies of blood samples of ethanol treated rats showed significant increase in the levels of serum enzyme activities, reflecting the liver injury caused by ethanol and blood samples from the animals treated with AEAC and AQEAC showed significant decrease in the levels of serum markers, indicating the protection of hepatic cells against ethanol induced hepatocellular injury. The effects of AEAC and AQEAC were comparable with standard drug silymarin.DOI: http://dx.doi.org/10.3329/icpj.v1i9.11619 International Current Pharmaceutical Journal 2012, 1(9): 279-284

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The Effectiveness of Tsu-San-Li (St-36) and Tai-Chung (Li-3) Acupoints for Treatment of Acute Liver Damage in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x01000253 ◽

2001 ◽

Vol 29 (02) ◽

pp. 221-226 ◽

Cited By ~ 11

Author(s):

Hsu-Jan Liu ◽

Sheng-Feng Hsu ◽

Chang-Chi Hsieh ◽

Tin-Yun Ho ◽

Ching-Liang Hsieh ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Acupuncture Therapy ◽

Liver Injury ◽

Acute Liver Injury ◽

Male Rats ◽

Acute Liver Damage ◽

Glutamate Pyruvate Transaminase ◽

Serum Glutamate Pyruvate Transaminase ◽

Glutamate Pyruvate ◽

Serum Glutamate

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-Sa-Li and Tai-Chung acupoints cannot prevent acute liver injury but may be effective in treating liver injury induced by carbon tetrachloride in rats.

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Hepatoprotective Effect of the Fruits of Polygonum orientale L. Against Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Natural Product Communications ◽

10.1177/1934578x20971501 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1934578X2097150

Author(s):

Yung-Jia Chiu ◽

Kun-Chang Wu ◽

Jen-Chieh Tsai ◽

Chun-Pin Kao ◽

Jung Chao ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Growth Factor ◽

Liver Injury ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Transforming Growth Factor Β ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Tissue Growth ◽

Factor Α

The aim of this study was to evaluate the hepatoprotective effects of the fruits of Polygonum orientale L. (POE) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury. Bioactive components of POE were identified using liquid chromatography (LC)-mass spectrometry (MS)/MS by comparison with standards. Treatment with either silymarin (200 mg/kg) or POE (0.5 and 1.0 g/kg) caused significant decreases in the serum levels of enzymes and reduced the extent of liver lesions and fibrosis in histological analysis. POE (0.5 and 1.0 g/kg) decreased the levels of malondialdehyde, nitric oxide, proinflammatory cytokines (ie, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6), an inflammatory cytokine (ie, cyclooxygenase-2), a profibrotic cytokine (ie, transforming growth factor-β), and fibrosis-related proteins (ie, connective tissue growth factor and α-smooth muscle actin) in the liver and enhanced the activities of the antioxidative enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. Quantitative analysis of the active constituents in POE revealed an extract composition of 3.4 mg/g of protocatechuic acid, 20.8 mg/g of taxifolin, and 5.6 mg/g of quercetin. We have demonstrated that the hepatoprotective mechanisms of POE are likely to be associated with the decrease in inflammatory cytokines by increasing the activities of antioxidant enzymes. Our findings provide evidence that POE possesses a hepatoprotective activity to ameliorate chronic liver injury.

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Evaluation of Hepatoprotective Activity of Clerodendrum paniculatum Leaf on Carbon Tetrachloride-Induced Liver Toxicity Model in Swiss Albino Rats and Its Characterization by GC-MS

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200312152331 ◽

2020 ◽

Vol 20 (7) ◽

pp. 1097-1109

Author(s):

Remya Kopilakkal ◽

Balamurali M. Musuvathi

Keyword(s):

Nitric Oxide ◽

Antioxidant Activity ◽

Carbon Tetrachloride ◽

Ethyl Acetate ◽

Ethyl Acetate Extract ◽

Hepatoprotective Activity ◽

Total Phenolic ◽

Bioactive Constituents ◽

Ms Analysis ◽

Serum Glutamate

Background: Clerodendrum paniculatum has ethnomedicinal importance in treatment of disorders like wound, typhoid, jaundice, malaria and anemia. Objective: To evaluate the antioxidant and hepatoprotective activity of Clerodendrum paniculatum leaves against carbon tetrachloride (CCl4) induced rat model and identification of its bioactive constituents by Gas Chromatography Mass Spectroscopy (GC MS). Methods: Successive solvent extraction was carried out. Total phenolic, flavonoid content and antioxidant activity by 2,2- diphenyl-1-picryl hydrazyl (DPPH), nitric oxide and 2-Azino-bis [3-ethyl benzothiazoline- 6-sufonic acid] (ABTS method) were done. Ethyl acetate extract was selected for hepatoprotective study in carbon tetrachloride intoxicated model followed by the measurement of liver function marker enzymes such as SGOT (Serum Glutamate Oxaloacetate Transaminase), SGPT (Serum Glutamate Pyruvate Transaminase), and ALP (Alkaline Phosphatase). Biochemical parameters like bilirubin and protein were measured. Histopathologic liver sections were carried out. Bioactive constituents were evaluated by GC MS. Results: By DPPH and ABTS method, ethyl acetate extract showed IC50 as 70.14±0.92 μg/ml,2958.24±2.460 μg/ml, respectively. The alcoholic extract showed maximum IC50 (197.22 ±7.16 μg/ml) by Nitric oxide radical scavenging method. Hepatoprotective study reveals that intoxicated animal groups have elevated levels of enzymes and bilirubin and suppress the production of protein. The extract pre-treatment showed a significant decrease in enzymes and increased production of total protein in a dose-dependent manner. Histopathologic studies also support the hepatoprotective activity. GC MS analysis revealed the presence of seven major bioactive constituents with ethyl palmitate as the major one. Conclusion: The results support the proof for the hepatoprotective potential of the CPLE extract with potent antioxidant activity and enhanced liver enzyme level. The observed activity could be due to the presence of bioactive compounds as identified by GC MS analysis.

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Effects and Mechanisms of Acremoniumterricola milleretal mycelium on Liver Fibrosis Induced by Carbon Tetrachloride in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009019 ◽

2011 ◽

Vol 39 (03) ◽

pp. 537-550 ◽

Cited By ~ 10

Author(s):

Xiao-Peng Tian ◽

Yan-Yan Yin ◽

Xia Li

Keyword(s):

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Liver Injury ◽

Chinese Herb ◽

Immunoblot Analysis ◽

Hepatoprotective Activity ◽

Protective Effects ◽

Sprague Dawley ◽

Procollagen Type ◽

Tgf Β1

Acremoniumterricola milleretal mycelium (AMM) is one of the most precious traditional Chinese medicines. It has numerous protective effects on organs, and has been used in Chinese herb prescription to treat refractory diseases. Our preliminary studies demonstrated that AMM had hepatoprotective activity in acute liver injury. We further investigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloride ( CCl 4) and explore its possible mechanisms. The animal model was established by injection with 50% CCl 4 subcutaneously in male Sprague-Dawley rats twice a week for eight weeks. Meanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day until sacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreased CCl 4-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl 4 treatment. Moreover, AMM (350 and 700 mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly. Immunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested that AMM could protect liver damage and inhibit the progression of hepatic fibrosis induced by CCl 4, and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.

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Evaluation of Hepatoprotective activity of Ethanolic Extract of Garuga pinnata Roxburgh leaves against Carbon tetrachloride induced Hepatotoxicity in rats.

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00419 ◽

2021 ◽

pp. 2375-2380

Author(s):

Sandeep Chavan ◽

Remeth Dias ◽

Chandrakant Magdum

Keyword(s):

Carbon Tetrachloride ◽

Biochemical Parameters ◽

Histopathological Examination ◽

Liquid Paraffin ◽

Ethanolic Extract ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Antioxidant Defense Enzymes ◽

Serum Glutamate

In this study we investigated the in vivo Hepatoprotective activity of ethanolic extract of Garuga pinnata (EEGP) leaves in Carbon tetrachloride (CCl4) induced hepatotoxicity using wistar rats of either sex as model. Hepatotoxicity was induced by the administration of CCl4 intraperitoneally (0.125ml CCl4 in liquid paraffin (1:1) per 100g body weight). Garuga pinnata leaves extract at different dose levels (200 and 400mg/kg, p.o.) showed the dose dependant hepatoprotective effect and was compared with well known standard hepatoprotective Silymarain (100mg/kg). When groups were treated with CCl4, significant increase in serum biochemical parameters such as Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline phosphate (ALP), Acid Phosphate (ACP), Creatinine and alteration of tissue biochemical parameters such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and the total proteins were observed. The histopathological examination of the CCl4 treated groups showed sinusoidal congestion, centrilobular necrosis, marked vacuolations and congestion. However, pretreatment with extract of leaves of Garuga pinnata significantly reduced the increased serum levels of biochemical parameters and restored antioxidant defense enzymes level to its normal. Moreover, histopathology of leaves extract treated groups showed normal architecture with minimal sinusoidal congestion. Taken together, our study concludes that EEGP to be a more potential agent for caring liver from CCl4 induced damage.

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Evaluation of Hepatoprotective Effect of Leaves ofCassia sopheraLinn.

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/436139 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Arijit Mondal ◽

Sanjay Kumar Karan ◽

Tanushree Singha ◽

D. Rajalingam ◽

Tapan Kumar Maity

Keyword(s):

Carbon Tetrachloride ◽

Total Protein ◽

Total Bilirubin ◽

Serum Alkaline Phosphatase ◽

Histopathological Examination ◽

Elevated Serum ◽

Hepatoprotective Activity ◽

Hepatic Damage ◽

Protein Levels ◽

Serum Glutamate

In the present study, the hepatoprotective activity of ethanolic extracts ofCassia sopheraLinn. leaves was evaluated against carbon-tetrachloride- (CCl4-) induced hepatic damage in rats. The extracts at doses of 200 and 400 mg/kg were administered orally once daily. The hepatoprotection was assessed in terms of reduction in histological damage, changes in serum enzymes, serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (ALP), total bilirubin, and total protein levels. The substantially elevated serum enzymatic levels of AST, ALT, ALP, and total bilirubin were restored towards the normalization significantly by the extracts. The decreased serum total protein level was significantly normalized. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate thatCassia sopheraleaves have potent hepatoprotective action against carbon tetrachloride-induced hepatic damage in rats. This study suggests that possible activity may be due to the presence of flavonoids in the extracts.

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Actinidia rubricaulisAttenuates Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x07004643 ◽

2007 ◽

Vol 35 (01) ◽

pp. 81-88 ◽

Cited By ~ 7

Author(s):

Jung-Chun Liao ◽

Kun-Hung Lin ◽

Hao-Yuan Cheng ◽

Jin-Bin Wu ◽

Ming-Tsuen Hsieh ◽

...

Keyword(s):

Antioxidant Activity ◽

Carbon Tetrachloride ◽

Liver Injury ◽

Experimental Period ◽

Hepatoprotective Effect ◽

Glutamate Pyruvate Transaminase ◽

Chronic Liver Injury ◽

Glutamate Pyruvate ◽

Ethanol Extracts ◽

Serum Glutamate

The purpose of this study was to evaluate the antioxidant activity and hepatoprotective effect of ethanol extracts of Actinidia rubricaulis (AR) on chronic liver injury induced by carbon tetrachloride ( CCl4) in rats. CCl4(20%, 0.5 ml/rat) was given twice a week for 8 weeks, and animals received AR throughout the entire experimental period. AR reduced the elevated levels of serum glutamate-oxalate-transaminase (sGOT) and glutamate-pyruvate-transaminase (sGPT) caused by CCl4at weeks 1,3,6, and 8. The biochemical data were consistent with those of the histological observations. The AR extract recovered the CCl4-induced liver injury and showed antioxidant effect in assays of antioxidant enzyme activity, such as SOD, GSH-Px and GSH-Rd. Based on these results, we suggest that the hepatoprotective effect of the AR is related to its antioxidant activity.

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