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

Author(s):  
Shah G. H. ◽  
Patel B. G. ◽  
Shah G. B.

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.

Author(s):  
Balakrishna Vuyyala ◽  
Lakshmi Thakkalapally

  Objective: The purpose of this study was to evaluate the effect of Terminalia chebula fruit extract on liver antioxidant enzymes in ethanol-induced hepatotoxicity in rats.Method: Rats were divided into six different groups each having six. Group 1 served as a control, Group 2 received 40% ethanol (2 ml/100 g, oral), in sterile water, Groups 4, 5, and 6 served as extract treatment groups and received 50, 100, and 200 mg/kg, orally, ethanolic fruit extract of T. chebula (TCE) and Group 3 served as standard group and received silymarin 25 mg/kg orally. All the treatment protocols followed 21 days, and after which rats were sacrificed, the liver was taken for antioxidant and histological studies, respectively.Results: The ethanol-treated group rats (G2) showed variable decrease in antioxidant parameter (catalase, glutathione, and glutathione reductase) levels. Administration of ethanolic TCE significantly prevented ethanol-induced elevation in the levels of malondialdehyde lipid peroxidation and decreased antioxidant parameters in experimental groups of rats. The effect of extract was compared with a standard drug, silymarin. The changes in antioxidant parameters were supported by histological profile.Conclusion: It is concluded that the ethanolic fruit TCE protects against ethanol-induced oxidative liver injury in rats.


Author(s):  
Bushra Hasan Khan ◽  
Farida Ahmad ◽  
Jameel Ahmad ◽  
Syed Mobashir Yunus

Objective: To evaluate the hepatoprotective effect of ethanolic extract of the root (REE) of Punica granatum.Methods: This study was conducted on adult albino Wistar rats of either sex weighing 150-200 g. Animals were divided into five groups (n=5). Liver injury was produced by carbon tetrachloride (CCl4) 1 ml/kg dissolved in olive oil (1:1) given intraperitoneally on day 1 and day 4 of the study duration of 14 days. Silymarin (50 mg/kg/d) orally was used as standard drug. Test groups received an REE of P. granatum (REE) at doses of 200 and 400 mg/kg/day orally along with CCl4. On the 15th day, all animals were sacrificed, and blood was collected. Liver was sent for histopathological examination. The hepatoprotective effect of REE was evaluated by assessment of physical parameters, histopathological examination and biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin.Results: The administration of REE of P. granatum at doses of 200 and 400 mg/kg/day orally, exhibited a highly significant decrease in the rise of mean serum AST, ALT, ALP, and total bilirubin as compared to CCl4 treated group (p<0.001). Histopathological examination of the liver also suggested hepatoprotective effect of REE of P. granatum by restoration of hepatic architecture toward normal. Decrease in the extent of centrilobular necrosis was observed in REE (200 and 400 mg/kg/day) treated rats when compared to CCl4 treated group.Conclusion: This study demonstrated hepatoprotective activity of REE of P. granatum against CCl4 induced liver injury in rats.


Author(s):  
Gopi H Shah ◽  
Bharat G Patel ◽  
Gaurang B Shah

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.


2018 ◽  
Vol 5 (2) ◽  
Author(s):  
Krishnakumar N M

The present study was designed to assess the possible hepatoprotective activity of the leaf ethanolic extract of coded plant (Code No. 222**) against carbon tetrachloride (CCl4)-induced hepatic injury in Wistar albino rats. The animals were divided into different groups and treated with 222 leaf ethanolic extract at different concentrations for five days. Silymarin, the known hepatoprotective standard compound (100 mg/kg) was administered for five days. Hepatotoxicity was induced by the subcutaneous administration of a single dose of CCl4: Olive oil (2 mL/kg) on days 2 and 3. The administration of CCl4 resulted in marked increase in serum hepatic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum bilirubin levels. CCl4 intoxication also resulted in a significant (P=0.05) increase in malondialdehyde (MDA), which is a common marker of lipid peroxidation. The other biochemical parameters such as cholesterol, triglycerides, creatinine, urea and uric acid levels were also increased significantly (P=0.05) compared to normal control group. Changes in serum hepatic enzymes, biochemical parameters and MDA levels induced by CCl4 were reversed by the leaf ethanolic extract of 222 (125 mg/kg) dose. The standard drug silymarin treated group also reversed CCl4-induced changes in biomarkers of liver function and MDA levels. Histopathological studies of the liver samples confirmed the hepatoprotective property of the coded drug 222. It was seen that histopathological damage induced by CCl4 were improved in rat liver, treated with 222 extract. The results of the present study suggested that coded plant (222) leaf ethanolic extract may be used as a hepatoprotective agent against toxic effects caused carbon tetrachloride in the liver.


2019 ◽  
Vol 9 (1) ◽  
pp. 5-11
Author(s):  
Geeta Deswal ◽  
Kumar Guarve ◽  
Priyanka Kriplani ◽  
Ashwani K. Dhingra ◽  
Bhawna Chopra ◽  
...  

Background: Literature reports numerous causes for liver damage, which mainly include viral hepatitis (most commonly hepatitis B), cirrhosis, cell stress, hepatic damage by NSAIDs or alcohol. In the present study, methanolic extracts of Tectona grandis leaves were evaluated for hepatoprotective activity against CCl4 induced liver damage in rats. Methods: Hepatic injury in rats was carried out using the CCl4-induced hepatotoxic model. Methanolic extracts of Tectona grandis were administered orally at two different doses (200mg/kg & 400mg/kg) daily. The biochemical parameters (SGOT, SGPT, ALP, and serum bilirubin) were estimated using Reitman and Frankel's method in addition Kind King’s method. Results: The preliminary phytochemical studies confirmed the existence of saponins, carbohydrates, tannins, and flavonoids. CCl4 treated group boost the concentrations of Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), Alkaline Phosphate (ALP) and serum bilirubin as compared to control group (rats treated with vehicle). The methanolic extract of plant (200 mg/kg & 400 mg/kg) and standard drug silymarin (100 mg/kg) produced a significant decrease in raised levels of these enzymes as compared to control. Conclusion: The results clearly indicate that Tectona grandis leaves have notable hepatoprotective activity in rats hepatic damage induced by CCl4.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Kannappan Poornima ◽  
Palanisamy Chella Perumal ◽  
Velliyur Kanniappan Gopalakrishnan

This study is an attempt to evaluate the hepatoprotective activity ofTabernaemontana divaricataagainst DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant ofTabernaemontana divaricataat doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use ofTabernaemontana divaricataextract in the treatment of carcinogen induced hepatic necrosis.


2003 ◽  
Vol 31 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Hyung-Sup Bae ◽  
Young-Suk Kim ◽  
Ki-Ho Cho ◽  
Kyung-Sup Lee ◽  
Jung-Jin Kim ◽  
...  

β-Glucuronidase-inhibitory and hepatoprotective effects of Reduohanxiao-tang (Yuldahanso-tang), which has been used for liver diseases and stroke, on carbon tetrachloride (CCl4)-induced hepatotoxicity of rats were investigated. Reduohanxiao-tang potently inhibited β-glucuronidases. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid dehydrogenase (LDH) levels of the CCl4 group orally treated with Reduohanxiao-tang (100 mg/kg) were lowered to 54%, 71.5% and 66.1% of the CCl4-treated control group, respectively. Among the ingredients of the Reduohanxiao-tang, the rhizomes of Pueraria thunbergiana and it Scutellaria baicalensis potently inhibited β-glucuronidases and protected against CCl4-induced liver injury. Orally administered puerarin, which is a main component of Pueraria thunbergiana, showed potent hepatoprotective activity, but did not inhibit β-glucuronidase. However, daidzein, which is produced from puerarin by human intestinal bacteria, potently inhibited β-glucuronidase. These results suggest that β-glucuronidase inhibition by herbal medicines may protect a gainst CCl4-induced liver injury.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Oytun Erbaş ◽  
Levent Akman ◽  
Altuğ Yavaşoğlu ◽  
Mustafa Cosan Terek ◽  
Tülay Akman ◽  
...  

Cisplatin (CP), an antitumor agent, has been shown to cause ovarian injury and dysfunction in both animal and human studies. The present study was conducted to investigate the protective effect of oxytocin (OT) on CP-induced ovarian toxicity in rats. Twenty-one adult female rats were included in the study. Fourteen rats were administered intraperitoneally CP (2 mg/kg/day) twice a week for 5 weeks. Control group (n=7) did not receive any treatment. Following treatment, CP-received rats were randomly divided into two groups and treated with either saline (1 mL/kg/day,n=7) or OT (160 μg/kg/day,n=7) for 5 weeks. Then, ovarian toxicity and effects of OT were evaluated by histomorphological and biochemical analysis. Our findings revealed a significant reduction in the number of follicles at each grade in saline-treated group. AMH level was significantly lower in saline group compared to control (P<0.0005). OT treatment significantly attenuated CP toxicity in ovaries and increased AMH levels compared to saline group (P<0.005). Also, administration of OT lessened lipid peroxidation and prevented glutathione depletion in CP-treated rats (P<0.05). These results indicated that OT could lessen the CP-induced ovarian damage and improve follicular reserve by preventing oxidative damage.


2017 ◽  
Vol 24 (02) ◽  
pp. 342-346
Author(s):  
Noor ul Ain ◽  
Nusrat Bano ◽  
Anwar Ejaz Beg ◽  
Kamran Hameed ◽  
Talha Bin Fayyaz ◽  
...  

Objectives: Oxaliplatin causes hematological toxicities in clinical setting whichlimits its efficacy. The aim of this study is to investigate the therapeutic effects of Andrographispaniculata against hematological toxicity caused by oxaliplatin. Study design: Experimentalanimal study. Period: Study takes 8 month from March 2015 to Oct 2015. Setting: Dow universityanimal house. Method: Wistar albino male rats, divided into 3 equals groups (n=6): GroupN* was a control group (0.9% normal saline), Group NP0 was Oxaliplatin treated group andGroup NP1 was prophylactically treated with Andrographis paniculata followed by Oxaliplatinin order to assess the protective effects of Andrographis paniculata against the hematologictoxicity caused by Oxaliplatin. Results: Prophylactic treatment with Andrographis paniculata(NP1) significantly increases the levels of platelets and neutrophile count compared with thestandard (NP0) (p<0.01) and increases the RBCs count and levels of hemoglobin comparedwith the standard (NP0). Conclusion: Prophylactic treatment with Andrographis paniculata(NP1) was effective in reducing risk of thrombocytopenia, anemia and neutropenia associatedwith Oxaliplatin.


2020 ◽  
Vol 9 (4) ◽  
pp. 333-338
Author(s):  
Marianne Marianne ◽  
Urip Harahap ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Chintya Monica Thampati ◽  
Herman Syukur Harefa

Introduction: Isoniazid (INH) and rifampin (RIF) are antituberculosis drugs that can induce injury in the liver. The purpose of this study was to investigate the antioxidant and hepatoprotective activities of the ethanol extract of Curcuma heyneana rhizome on liver injury in animal model induced by INH and RIF. Methods: Antioxidant activity was measured by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. All animals were divided into 7 groups. Liver injury was induced by using combination of INH at the dose of 50 mg/kg and RIF at the dose of 100 mg/kg. These drugs were administrated for 15 days along with extracts at doses of 5, 25, 125 or 625 mg/kg. Positive control group was given catechin. On the 16th day, the rats were sacrificed, blood and livers were collected for assessment of biochemical parameters like alanine transaminase (ALT) and aspartate transaminase (AST) and histological studies, respectively. Results: The ethanol extract strongly scavenged DPPH with inhibition concentration 50 (IC50) of 82.48 ppm. Administration of ethanol extract of C. heyneana rhizome at the dose of 25, 125 or 625 mg/kg significantly inhibited the elevation of AST and ALT (P<0.01). Moreover, the effects caused by administration of the extracts were similar to the effects caused by catechins. Various doses of the extract could effectively reduce tissue damage. Conclusion: This result suggests that ethanol extract of C. heyneana rhizome at the doses of 25, 125 and 625 mg/kg might be effective as hepatoprotective agent.


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