Toxicology International (Formerly Indian Journal of Toxicology)

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Evaluation of Hepatoprotective Activity of Ethanolic Extract of Aerial Parts of Premna tomentosa against Paracetamol-Induced Liver Toxicity on Wistar Rats


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1 Dept. of Pharmacology, Mahatma Gandhi Medical College & Research Institute, Puducherry, India
     

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Hepatoprotective activity of ethanolic extract of aerial parts of Premna tomentosa were evaluated against paracetamol-induced liver toxicity and comparison to the standard hepatoprotectant, silymarin. Thirty male wistar albino rats were randomised into five groups with six rats in each group. Group A&B sereved as normal control and toxic control respectively, and were administered normal saline. Group C& D were treated with ethanolic extract of Premna tomentosa at doses 100mg/kg and 200mg/kg respectively. Group E was treated with the standard drug Silymarin 25mg/kg. Toxicity was induced in all the groups except the first by giving Paracetamol at 2g/kg on the 5th day. All the rats were treated for 7 days and after the last dosing the rats were fasted for 24hrs and sacrificed. Serum was sent for biochemical analysis for assaying liver profile. Histopathology and antioxidant studies were done on liver. In our study ethanolic extract Premna tomentosa showed beneficial effect on paracetamol induced liver toxicity which was evident by the significant improvement in liver profile consisting of AST, ALT, ALP, GGT, total cholesterol, total protein, triglycerides and total bilirubin in a dose dependent manner, which is consistent with the histopathological findings. Increase in GSH and Catalase and decrease in TBARS validates the antioxidant property of the extract. The study has proved that Premna tomentosa posses a significant hepatoprotective activity which was comparable to the standard drug silymarin. It warrants further study in humans before including it in the prevention of hepatotoxicity.

Keywords

Premna tomentosa, Paracetamol, Hepatoprotective, Antioxidant.
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  • Devarbhavi H. An Update on Drug-induced Liver Injury. J ClinExpHepatol. 2012 Sep;2(3):247–59.

  • Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105(11):2396–404.

  • Myers RP, Shaheen AAM, Li B, Dean S, Quan H. Impact of liver disease, alcohol abuse, and unintentional ingestions on the outcomes of acetaminophen overdose. ClinGastroenterolHepatol Off ClinPract J Am Gastroenterol Assoc. 2008;6(8):918–25.

  • Chan K. Some aspects of toxic contaminants in herbal medicines. Chemosphere. 2003;52(9):1361–71.

  • Mahanta M, Mukherjee AK. Neutralisation of lethality, myotoxicity and toxic enzymes of Najakaouthia venom by Mimosa pudica ischolar_main extracts. J Ethnopharmacol. 2001;75(1):55–60.

  • CPCSEA. CPCSEA Guidelines for laboratory animal facility. Indian J Pharmacol. 2003;35(4):257–74.

  • OECD. Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure [Internet]. Paris: Organisation for Economic Co-operation and Development; 2008 [cited 2015 Sep 24]. Available from: http://www.oecd-ilibrary.org/content/book/9789264071049-en

  • Chattopadhyay RR. Possible mechanism of hepatoprotective activity of Azadirachtaindica leaf extract: part II. J Ethnopharmacol. 2003;89(2-3):217–9.

  • McClure DE. Clinical pathology and sample collection in the laboratory rodent. Vet Clin North Am ExotAnim Pr. 1999;2(3):565–90.

  • Reitman S, Frankel S. In vitro determination of transaminase activity in serum. Am J ClinPathol. 1957;28:56–64.

  • Kind PRN, King EJ. Estimation of Plasma Phosphatase by Determination of Hydrolysed Phenol with Amino-antipyrine. J ClinPathol. 1954;7(4):322–6.

  • Szasz G. A kinetic photometric method for serum gammaglutamyltranspeptidase. Clin Chem. 1969;15(2):124–36.

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.

  • Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974 Apr;20(4):470–5.

  • Helga Tait Malloy KAE. The Determination of Bilirubin with the Photoelectric Colorimeter. J Biol Chem. 1937;119(2):481–90.

  • L B Foster RTD. Stable reagents for determination of serum triglycerides by colorimetric Hatzsch condensation method. Clin Chem. 1973;19(3):338–40.

  • Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.

  • Ellman GL. Tissue sulfhydryl groups. Arch BiochemBiophys. 1959;82(1):70–7.

  • Luck H. Catalase. Methods Enzym Anal. 1965;885–8.

  • Carleton HM, Drury RAB, Wallington EA. General staining procedures. In: Carleton’s Histological technique. 5th ed. New York: Oxford University Press; 1980. p. 147–8.

  • Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem. 2000 Dec;46(12):2050–68.

  • Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008;245(3):194–205.

  • Reuben A. Hy’s law. Hepatology. 2004 Feb 1;39(2):574–8.

  • Sheehan M, Haythorn P. Predictive values of various liver function tests with respect to the diagnosis of liver disease. ClinBiochem. 1979;12(6):262–3.

  • Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr. 2007;74(7):663–71.

  • Potter WZ, Thorgeirsson SS, Jollow DJ, Mitchell JR. Acetaminopheninduced hepatic necrosis V. Correlation of hepatic necrosis, covalent binding and glutathione depletion in hamsters. Pharmacology. 1974;12(3):129–43.

  • Zaher H, Buters JTM, Ward JM, Bruno MK, Lucas AM, Stern ST, et al. Protection against Acetaminophen Toxicity in CYP1A2 and CYP2E1 Double-Null Mice. ToxicolApplPharmacol. 1998;152(1):193–9.

  • Pandima Devi K, Devaki T. Protective effect of Premna tomentosa on acetaminophen-induced acute hepatitis in rats. Med Sci Res. 1998;26(11):785–7.

  • Pandima Devi K, Sreepriya M, Balakrishna K, Devaki T. Protective effect of Premna tomentosa (L. Verbenaceae) extract on membrane-bound phosphatases and inorganic cations transport in acetaminophen-induced hepatotoxicity rats. J Ethnopharmacol. 2004;93(2–3):371–5.

  • Hari Prasad K, Jayalakshmi R, Chandrakasan G. Inhibitory effect of premna tomentosa (l. Verbenaceae) on stellate cell activation and collagen accumulation in dmn induced hepatifibrosis in rats. Biomedicine. 2006;26(3, 4):34–42.

  • Calleja MA, Vieites JM, Montero-Meterdez T, Torres MI, Faus MJ, Gil A, et al. The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br J Nutr. 2013;109(03):394–401.

  • McIntyre N. Plasma lipids and lipoproteins in liver disease. Gut. 1978;19(6):526–30.

  • Muller P, Fellin R, Lambrecht J, Agostini B, Wieland H, Rost W, et al. Hypertriglyceridaemia Secondary to Liver Disease. Eur J Clin Invest. 1974 Feb 1;4(1):419–28.

  • Devi KP, Sreepriya M, Balakrishna K, Veluchamy G, Devaki T. Assessment of the Protective Potential of Premna tomentosa (L. Verbenaceae) Extract on Lipid Profile and Lipid-Metabolizing Enzymes in Acetaminophen-Intoxicated Rats. J Altern Complement Med. 2004;10(3):540–6.

  • Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free RadicBiol Med. 1990;9(6):515–40.

  • Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J PharmacolExpTher. 1973;187(1):211–7.

  • Devi KP, Sreepriya M, Balakrishna K, Devaki T. Protective effect of Premna tomentosa extract (L. verbanacae) on acetaminopheninduced mitochondrial dysfunction in rats. Mol Cell Biochem. 2005;272(1-2):171–7.

  • Muriel P, Garciapiña T, Perez-Alvarez V, Mourelle M. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J ApplToxicol. 1992;12(6):439–42.

  • Reicks MM, Crankshaw D. Effects of D-limonene on hepatic microsomal monooxygenase activity and paracetamol-induced glutathione depletion in mouse. Xenobiotica. 1993;23(7):809–17.

  • Chance B, Greenstein DS, Roughton FJW. The mechanism of catalase action. I. Steady-state analysis. Arch BiochemBiophys. 1952;37(2):301–21.

  • Zhang X, Ouyang J, Thung SN. Histopathologic manifestations of drug-induced hepatotoxicity. Clin Liver Dis. 2013 Nov;17(4):547–64.

  • Blazka ME, Elwell MR, Holladay SD, Wilson RE, Luster MI. Histopathology of acetaminophen-induced liver changes: role of interleukin 1 alpha and tumor necrosis factor alpha. ToxicolPathol. 1996 Apr;24(2):181–9.

  • Guguloth S, Vivekanandan L, Singaravel S, Sheik HS, Thangavel S. Hepatoprotective activity of Vitexnegundo Linn bark against chemical induced toxicity in experimental rats. Pharmanest. 2011;2(5-6):534–41.

  • Girish C, Koner BC, Jayanthi S, Ramachandra Rao K, Rajesh B, Pradhan SC. Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice. FundamClinPharmacol. 2009;23(6):735–45.


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  • Evaluation of Hepatoprotective Activity of Ethanolic Extract of Aerial Parts of Premna tomentosa against Paracetamol-Induced Liver Toxicity on Wistar Rats

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Authors

M. Mano Jervin
Dept. of Pharmacology, Mahatma Gandhi Medical College & Research Institute, Puducherry, India
G. Somasundaram
Dept. of Pharmacology, Mahatma Gandhi Medical College & Research Institute, Puducherry, India
R. Sudarcodi
Dept. of Pharmacology, Mahatma Gandhi Medical College & Research Institute, Puducherry, India
K. Manimekalai
Dept. of Pharmacology, Mahatma Gandhi Medical College & Research Institute, Puducherry, India

Abstract


Hepatoprotective activity of ethanolic extract of aerial parts of Premna tomentosa were evaluated against paracetamol-induced liver toxicity and comparison to the standard hepatoprotectant, silymarin. Thirty male wistar albino rats were randomised into five groups with six rats in each group. Group A&B sereved as normal control and toxic control respectively, and were administered normal saline. Group C& D were treated with ethanolic extract of Premna tomentosa at doses 100mg/kg and 200mg/kg respectively. Group E was treated with the standard drug Silymarin 25mg/kg. Toxicity was induced in all the groups except the first by giving Paracetamol at 2g/kg on the 5th day. All the rats were treated for 7 days and after the last dosing the rats were fasted for 24hrs and sacrificed. Serum was sent for biochemical analysis for assaying liver profile. Histopathology and antioxidant studies were done on liver. In our study ethanolic extract Premna tomentosa showed beneficial effect on paracetamol induced liver toxicity which was evident by the significant improvement in liver profile consisting of AST, ALT, ALP, GGT, total cholesterol, total protein, triglycerides and total bilirubin in a dose dependent manner, which is consistent with the histopathological findings. Increase in GSH and Catalase and decrease in TBARS validates the antioxidant property of the extract. The study has proved that Premna tomentosa posses a significant hepatoprotective activity which was comparable to the standard drug silymarin. It warrants further study in humans before including it in the prevention of hepatotoxicity.

Keywords


Premna tomentosa, Paracetamol, Hepatoprotective, Antioxidant.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi2%2F146685