Skip to main content
Top
Published in: Clinical Phytoscience 1/2018

Open Access 01-12-2018 | Original contribution

Hepatoprotective potentials of methanol extract of T. conophorum seeds of carbon tetrachloride induced liver damage in Wistar rats

Authors: Kelly Oriakhi, Patrick O. Uadia, Ikechi G. Eze

Published in: Clinical Phytoscience | Issue 1/2018

Login to get access

Abstract

Background

Tetracarpidium conophorum (TC) is a tropical plant used in ethno medicine for treating various diseases including hepatic ailments. The present study investigated the effect of methanol extract of T. conophorum seeds in rats intoxicated with CCl4 24 h and 48 h after intoxication respectively.

Methods

Thirty-five male Wistar rats were distributed equally into seven groups. Group IA (control) received distilled water and olive oil (i.p), group IIA rats were intoxicated with CCl4 in olive oil (600 mg/kg, i.p.) only on the 8th day, while groups IIIA, IVA and VA were given 100 mg/kg of sylimarin, 250 mg/kg and 500 mg/kg of methanol extract respectively for 7 days, thereafter they were intoxicated with CCl4 on the 8th day. Groups VIA and VIIA were intoxicated with CCl4 on the 8th day and administered 250 mg/kg and 500 mg/kg of methanol extract of T. conophorum seeds at 1 h, 6 h, 12 h, 18 h and 24 h and the animals were sacrificed 24 h after intoxication with CCl4.This procedure was repeated for a different set of thirty-five (groups IB-VIIB) male rats but the animals were sacrificed 48 h after intoxication with CCl4. Fasting blood sample was collected by cardiac puncture for biochemical analyses.

Results

There were significant increases (p˂0.05) in serum hepatic enzyme markers (ALT, AST, ALP, and γ-GT) activities, as well as bilirubin and significant reduction in antioxidant enzymes (P˂0.05) in rats intoxicated with CCl4 when compared to control group, but administration (pre-treatment and post-treatment) of methanol extract of T. conophorum seeds at doses of 250 and 500 mg/kg body weight and standard sylimarin drug attenuated the toxic insult of CCl4 in a dose-dependent manner at 24 h and 48 h after intoxication respectively.

Conclusions

Our findings confirm that methanol extract of TC exhibited hepatoprotective activity against CCl4 induced liver damage.
Literature
1.
go back to reference Juza RM, Pauli EM. Clinical and surgical anatomy of the liver: a review for clinicians. Clin Anat. 2014;27:764–9.CrossRefPubMed Juza RM, Pauli EM. Clinical and surgical anatomy of the liver: a review for clinicians. Clin Anat. 2014;27:764–9.CrossRefPubMed
3.
go back to reference Raucy JL, Kramer JC, Lasker JM. Bioactivation of halogenated hydrocarbons by cytochrome P450 2E1. CRC Crit Rev Toxicol. 1993;23:1–20.CrossRef Raucy JL, Kramer JC, Lasker JM. Bioactivation of halogenated hydrocarbons by cytochrome P450 2E1. CRC Crit Rev Toxicol. 1993;23:1–20.CrossRef
4.
go back to reference Weber LW, Boll M, Stamp FA. Hepatotoxicity and mechan- ism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(3):105–36.CrossRefPubMed Weber LW, Boll M, Stamp FA. Hepatotoxicity and mechan- ism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(3):105–36.CrossRefPubMed
5.
go back to reference Mehendale HM, Roth RA, Gandolfi RA, Klaunig JE, Lemasters JJ, Curtis LR. Novel mechanisms in chemically induced hepatotoxicity. FASEB J. 1994;8:1285–95.CrossRefPubMed Mehendale HM, Roth RA, Gandolfi RA, Klaunig JE, Lemasters JJ, Curtis LR. Novel mechanisms in chemically induced hepatotoxicity. FASEB J. 1994;8:1285–95.CrossRefPubMed
6.
go back to reference Boll M, Weber LW, Becker E, Stampfl A. Mechanism of carbon tetrachloride induced hepatotoxicity. Hepatocellu- Lar damage by reactive carbon tetrachloride metabolites. Z Naturforsch. 2001;56(7–8):649–59.CrossRef Boll M, Weber LW, Becker E, Stampfl A. Mechanism of carbon tetrachloride induced hepatotoxicity. Hepatocellu- Lar damage by reactive carbon tetrachloride metabolites. Z Naturforsch. 2001;56(7–8):649–59.CrossRef
7.
go back to reference Sevanian A, Ursini G. Lipid peroxidation in membrane and low-density lipoproteins: similarities and differences. Free Rad Biol Med. 2000;29:306–11.CrossRefPubMed Sevanian A, Ursini G. Lipid peroxidation in membrane and low-density lipoproteins: similarities and differences. Free Rad Biol Med. 2000;29:306–11.CrossRefPubMed
8.
go back to reference Gallucci RM, Simeonova PP, Toriumi W, Luster MI. TNF-α regulates transforming growth factor-α expression in regenerating murine liver and isolated hepatocytes. J Immunol. 2000;164:872–8.CrossRefPubMed Gallucci RM, Simeonova PP, Toriumi W, Luster MI. TNF-α regulates transforming growth factor-α expression in regenerating murine liver and isolated hepatocytes. J Immunol. 2000;164:872–8.CrossRefPubMed
9.
go back to reference Gruebele A, Zawaski K, Kaplan D, Novak RF. Cytochrome P450 2E1– and cytochrome P450 2B1/2B2–catalyzed carbon tetrachloride metabolism: effects on signal transduction as demonstrated by altered immediate-early (c-Fos and c-Jun) gene expression and nuclear AP-1 and NF-κB transcription factor levels. Drug Metabol Disp. 1996;24:15–22. Gruebele A, Zawaski K, Kaplan D, Novak RF. Cytochrome P450 2E1– and cytochrome P450 2B1/2B2–catalyzed carbon tetrachloride metabolism: effects on signal transduction as demonstrated by altered immediate-early (c-Fos and c-Jun) gene expression and nuclear AP-1 and NF-κB transcription factor levels. Drug Metabol Disp. 1996;24:15–22.
10.
go back to reference Bak J, Je NK, Chung HY, Yokozawa T, Yoon S, Moon JO. Oligonol ameliorates CCl4-induced liver injury in rats via the NF-Kappa B and MAPK signaling pathways. Oxid Med Cell Longev. 2016;1:1–12. Bak J, Je NK, Chung HY, Yokozawa T, Yoon S, Moon JO. Oligonol ameliorates CCl4-induced liver injury in rats via the NF-Kappa B and MAPK signaling pathways. Oxid Med Cell Longev. 2016;1:1–12.
11.
go back to reference Nieto N, Dominguez-Rosales JA, Fontana L, Salazar A, Armendariz-Borunda J, Greenwel P, Rojkind M. Rat hepatic stellate cells contribute to the acute-phase response with increased expression of alpha1(I) and alpha1(IV) collagens, tissue inhibitor of metallo-proteinase-1, and matrix-metalloproteinase-2 messenger RNAs. Hepatol. 2000;33:597–607.CrossRef Nieto N, Dominguez-Rosales JA, Fontana L, Salazar A, Armendariz-Borunda J, Greenwel P, Rojkind M. Rat hepatic stellate cells contribute to the acute-phase response with increased expression of alpha1(I) and alpha1(IV) collagens, tissue inhibitor of metallo-proteinase-1, and matrix-metalloproteinase-2 messenger RNAs. Hepatol. 2000;33:597–607.CrossRef
12.
go back to reference Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest. 1995;96:2461–8.CrossRefPubMedPubMedCentral Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest. 1995;96:2461–8.CrossRefPubMedPubMedCentral
13.
go back to reference Karou D, Dicko MH, Simpore J, Traore AS. Antioxidant and antibacterial activities of polyphenols from ethnomedicinal plants of Burkina Faso. Afri J Biotechnol. 2005;4:823–8. Karou D, Dicko MH, Simpore J, Traore AS. Antioxidant and antibacterial activities of polyphenols from ethnomedicinal plants of Burkina Faso. Afri J Biotechnol. 2005;4:823–8.
14.
go back to reference Wolf AT, Maurer R, Glickman J, Grace ND. Hepatic venous pressure gradient supplements liver biopsy in the diagnosis of cirrhosis. J Clin Gastroenterol. 2008;42:199–203.CrossRefPubMed Wolf AT, Maurer R, Glickman J, Grace ND. Hepatic venous pressure gradient supplements liver biopsy in the diagnosis of cirrhosis. J Clin Gastroenterol. 2008;42:199–203.CrossRefPubMed
15.
go back to reference Abbas KS, Xiaoqin T, Ridhwi M, Huaping Z, Barbara NT, Mark SC. Withaferin a, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma. J Nat Prod. 2010;73:1476–81.CrossRef Abbas KS, Xiaoqin T, Ridhwi M, Huaping Z, Barbara NT, Mark SC. Withaferin a, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma. J Nat Prod. 2010;73:1476–81.CrossRef
16.
go back to reference Oke OL. Leaf protein research in Ibadan, Nigeria. University of Ibadan Press; 1995. Oke OL. Leaf protein research in Ibadan, Nigeria. University of Ibadan Press; 1995.
17.
go back to reference Uadia PO, Oriakhi K, Osemwenkae PO, Emokpae MA. Effect of methanolic extract of Tetracarpidium conophorum seed on haematological parameters in carbon tetrachloride administered albino rats. Nig J Biochem Mol Bio. 2012b;27(1):63–5. Uadia PO, Oriakhi K, Osemwenkae PO, Emokpae MA. Effect of methanolic extract of Tetracarpidium conophorum seed on haematological parameters in carbon tetrachloride administered albino rats. Nig J Biochem Mol Bio. 2012b;27(1):63–5.
18.
go back to reference Ajaiyeoba EO, Fadare DA. Antimicrobial potential of extracts and fractions of the African walnut-Tetracarpidium conophorum. Afr J Biotechnol. 2006;5(22):2322–5. Ajaiyeoba EO, Fadare DA. Antimicrobial potential of extracts and fractions of the African walnut-Tetracarpidium conophorum. Afr J Biotechnol. 2006;5(22):2322–5.
19.
go back to reference Herbert JR, Hurley TG, Olendzki BC, Teas J, Ma Y, Ha JS. Nutritional and socioeconomic factors in reaction to prostate cancer mortality: a cross-national study. J Nat Cancer Inst. 1998;90:1637–47.CrossRef Herbert JR, Hurley TG, Olendzki BC, Teas J, Ma Y, Ha JS. Nutritional and socioeconomic factors in reaction to prostate cancer mortality: a cross-national study. J Nat Cancer Inst. 1998;90:1637–47.CrossRef
20.
go back to reference NIH. Guidelines for the care and use of laboratory animals. NIH publication No. 85–23, Revised 1985. 1985 NIH. Guidelines for the care and use of laboratory animals. NIH publication No. 85–23, Revised 1985. 1985
21.
go back to reference Reitman S, Frankel S. A colorimetric method for the determination of serum glutamate-oxaloacetate and pyruvate transaminass. Am J Clin Pathol. 1957;28:56–63.CrossRefPubMed Reitman S, Frankel S. A colorimetric method for the determination of serum glutamate-oxaloacetate and pyruvate transaminass. Am J Clin Pathol. 1957;28:56–63.CrossRefPubMed
22.
go back to reference Teitz NN. Determination of Gamma glutamyl Transferase. In: Fundamentals of clinical chemistry ed 3 Philadelphia, W. B Saunders Co: 1987; pg 391. Teitz NN. Determination of Gamma glutamyl Transferase. In: Fundamentals of clinical chemistry ed 3 Philadelphia, W. B Saunders Co: 1987; pg 391.
23.
go back to reference Kochmar JF, Moss DW. Determination of alkaline phosphatase. In: Tietz NW, editor. Fundamentals of clinical chemistry. Philadelphia: W.B. Saunders and company; 1976. p. 604. Kochmar JF, Moss DW. Determination of alkaline phosphatase. In: Tietz NW, editor. Fundamentals of clinical chemistry. Philadelphia: W.B. Saunders and company; 1976. p. 604.
24.
go back to reference Tietz NW, editor. Clinical Guide to Laboratory Tests. 3rd ed. Philadelphia: W.B. Saunders; 1995. Tietz NW, editor. Clinical Guide to Laboratory Tests. 3rd ed. Philadelphia: W.B. Saunders; 1995.
25.
go back to reference Jendrassik L, Grof P. Determination of direct and indirect bilirubin. Biochem Z. 1938;297:81. Jendrassik L, Grof P. Determination of direct and indirect bilirubin. Biochem Z. 1938;297:81.
26.
go back to reference Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for Superoxide dismustase. J Biol Chem. 1972;247:3170–5.PubMed Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for Superoxide dismustase. J Biol Chem. 1972;247:3170–5.PubMed
27.
28.
go back to reference Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61:882–8.PubMed Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61:882–8.PubMed
29.
go back to reference Habig WH, Pabst MJ, Jacoby WB. Glutathione-S-transferase, the first enzymatic step in mercaptroic acid formation. J Biol Chem. 1974;249:7130–9.PubMed Habig WH, Pabst MJ, Jacoby WB. Glutathione-S-transferase, the first enzymatic step in mercaptroic acid formation. J Biol Chem. 1974;249:7130–9.PubMed
30.
go back to reference Rostruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Sci. 1973;179:588–90.CrossRef Rostruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Sci. 1973;179:588–90.CrossRef
31.
go back to reference Varshney R, Kale RK. Effect of calmodulin antagonists on radiation induced lipid peroxidation in microsomes. Int J Rad Biol. 1990;58:733–43.CrossRefPubMed Varshney R, Kale RK. Effect of calmodulin antagonists on radiation induced lipid peroxidation in microsomes. Int J Rad Biol. 1990;58:733–43.CrossRefPubMed
33.
go back to reference Akindele AJ, Ezenwanebe KO, Anunobi CC, Adeyemi OO. Hepatoprotective and in vivo antioxidant effects of Byrsocarpus coccineus Schum and Thonn. (Connaraceae). J. Ethnopharmacol. 2010;129(1):46–52.CrossRef Akindele AJ, Ezenwanebe KO, Anunobi CC, Adeyemi OO. Hepatoprotective and in vivo antioxidant effects of Byrsocarpus coccineus Schum and Thonn. (Connaraceae). J. Ethnopharmacol. 2010;129(1):46–52.CrossRef
34.
go back to reference Jaishree V, Badami S. Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against D-galactosamine induced acute liver damage in rats. J Ethnopharmacol. 2010;130:103–6.CrossRefPubMed Jaishree V, Badami S. Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against D-galactosamine induced acute liver damage in rats. J Ethnopharmacol. 2010;130:103–6.CrossRefPubMed
35.
go back to reference Karakus E, Karadeniz A, Simsek N. Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4). J Hazard Mater. 2011;195:208–13.CrossRefPubMed Karakus E, Karadeniz A, Simsek N. Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4). J Hazard Mater. 2011;195:208–13.CrossRefPubMed
36.
go back to reference Waller RL, Glende EA, Recknagel RO. CCl4 and bromotrichloromethane toxicity. Dual role of covalent binding of metabolic cleavage products and lipid peroxidation in depression of microsomal calcium sequestration. Biochem Pharmacol. 1983;32:1613–7.CrossRefPubMed Waller RL, Glende EA, Recknagel RO. CCl4 and bromotrichloromethane toxicity. Dual role of covalent binding of metabolic cleavage products and lipid peroxidation in depression of microsomal calcium sequestration. Biochem Pharmacol. 1983;32:1613–7.CrossRefPubMed
38.
go back to reference Navarro VJ, Senior JR. Drug related hepatotoxicity. New England J Med. 2006;354:731–9.CrossRef Navarro VJ, Senior JR. Drug related hepatotoxicity. New England J Med. 2006;354:731–9.CrossRef
39.
go back to reference Kaplan MM. Serum alkaline phosphatase-another piece is added to the puzzle. Hepatol. 1986;6:526–8.CrossRef Kaplan MM. Serum alkaline phosphatase-another piece is added to the puzzle. Hepatol. 1986;6:526–8.CrossRef
40.
go back to reference Bulle F, Mavier P, Zafrani ES. Mechanism of gammaglutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach. Hepatol. 1990;11:545–50.CrossRef Bulle F, Mavier P, Zafrani ES. Mechanism of gammaglutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach. Hepatol. 1990;11:545–50.CrossRef
41.
go back to reference Eidi A, Mortazavi P, Moghadam JZ, Mousar P. Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats. Pharm Bio. 2014;1:1–10. Eidi A, Mortazavi P, Moghadam JZ, Mousar P. Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats. Pharm Bio. 2014;1:1–10.
42.
go back to reference Uadia PO, Oriakhi K, Osemwenkae PO, Emokpae MA. Phytochemical screening and antioxidant capacity of methanolic extract of Tetracarpidium conophorum seeds. Nig J Biochem and Mol Bio. 2012a;27(1):16–26. Uadia PO, Oriakhi K, Osemwenkae PO, Emokpae MA. Phytochemical screening and antioxidant capacity of methanolic extract of Tetracarpidium conophorum seeds. Nig J Biochem and Mol Bio. 2012a;27(1):16–26.
43.
go back to reference Aruoma OI. Free radical, antioxidants and international nutrition. Asia Pasific J Clin Nutr. 1999;8(1):53–63.CrossRef Aruoma OI. Free radical, antioxidants and international nutrition. Asia Pasific J Clin Nutr. 1999;8(1):53–63.CrossRef
44.
go back to reference Kamalakkannan N, Rukkumani R, Aruna K, Varma PS, Viswanathan P, Menon VP. Protective effect of N-acetyl cysteine in carbon tetrachloride-induced liver damage. Iranian J Pharm and ther. 2005;42:118–23. Kamalakkannan N, Rukkumani R, Aruna K, Varma PS, Viswanathan P, Menon VP. Protective effect of N-acetyl cysteine in carbon tetrachloride-induced liver damage. Iranian J Pharm and ther. 2005;42:118–23.
45.
go back to reference Martín MA, Ramos S, Granado-Serrano AB, RodríguezRamiro I, Trujillo M, Bravo L, Goya L. Hydroxytyrosol induces antioxidant/detoxificant enzymes and Nrf2 translocation via extracelular regulated kinases and phosphatidylinositol-3kinase/protein kinase B pathways in HepG2 cells. Mol Nutr Food Res. 2010;54:956–66.CrossRefPubMed Martín MA, Ramos S, Granado-Serrano AB, RodríguezRamiro I, Trujillo M, Bravo L, Goya L. Hydroxytyrosol induces antioxidant/detoxificant enzymes and Nrf2 translocation via extracelular regulated kinases and phosphatidylinositol-3kinase/protein kinase B pathways in HepG2 cells. Mol Nutr Food Res. 2010;54:956–66.CrossRefPubMed
46.
go back to reference Echeverria F, Ortiz M, Valenzuela R, Videla LA. Hydroxytyrosol and cytoprotection: a projection for clinical interventions. Int J Mol Sci. 2017;18:930.CrossRefPubMedCentral Echeverria F, Ortiz M, Valenzuela R, Videla LA. Hydroxytyrosol and cytoprotection: a projection for clinical interventions. Int J Mol Sci. 2017;18:930.CrossRefPubMedCentral
47.
go back to reference Theophile D, Emery TD, Desire DDP, Veronique PB, Njikam N. Effects of Alafia multiflora staff on lipid peroxidation and antioxidant enzyme status in carbon tetrachloride-treated rats. Pharmacol Online. 2006;2:76–8. Theophile D, Emery TD, Desire DDP, Veronique PB, Njikam N. Effects of Alafia multiflora staff on lipid peroxidation and antioxidant enzyme status in carbon tetrachloride-treated rats. Pharmacol Online. 2006;2:76–8.
Metadata
Title
Hepatoprotective potentials of methanol extract of T. conophorum seeds of carbon tetrachloride induced liver damage in Wistar rats
Authors
Kelly Oriakhi
Patrick O. Uadia
Ikechi G. Eze
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Clinical Phytoscience / Issue 1/2018
Electronic ISSN: 2199-1197
DOI
https://doi.org/10.1186/s40816-018-0085-8

Other articles of this Issue 1/2018

Clinical Phytoscience 1/2018 Go to the issue