Skip to main content
Top
Published in: Comparative Clinical Pathology 3/2020

01-06-2020 | Hepatocellular Carcinoma | Original Article

Evaluation of the hepatoprotective effect of oral administration of aqueous fraction of methanolic extract of Costus afer leaves during induction of hepatocellular carcinoma with diethylnitrosamine in rats

Authors: Godswill N. Anyasor, Damilola P. Idowu, Williams Nabofa

Published in: Comparative Clinical Pathology | Issue 3/2020

Login to get access

Abstract

This study evaluated the hepatoprotective effect of oral administration of aqueous fraction of methanolic extract of Costus afer leaves (CALAF) during induction of hepatocellular carcinoma (HCC) with diethylnitrosamine (DEN) in rats. The methanolic leaf extract was fractionated into hexane, ethyl acetate, butanol, and aqueous fractions. The in vitro antioxidant potential of the fractions were estimated by the assays of 2,2-diphenyl-1-picrylhydrazine and nitric oxide radical scavenging activity, ferric-reducing antioxidant potential, and total antioxidant capacity. CALAF had the most antioxidant effect. Rats were orally pretreated daily with CALAF at 100, 200, and 400 mg/kg or silymarin (hepatoprotective drug) at 50 mg/kg from 2 weeks prior to HCC induction and through 6 weeks of HCC induction. The HCC induction was by a single intraperitoneal injection of DEN at 200 mg/kg as an initiator, followed 2 weeks later by daily oral administration of 2-acetylaminofluorene at 30 mg/kg as promoter. At the end of HCC induction, levels of alpha-fetoprotein (AFP), liver function and antioxidants, gamma histone 2A family member X (γH2AX), and O6-methylguanine-DNA methyltransferase (MGMT) expressions were determined. HCC rats treated with CALAF at all doses had significantly (p < 0.05) reduced levels of AFP, aspartate aminotransferase, alanine aminotransferase, superoxide dismutase, glutathione peroxidase, reduced glutathione, and γH2AX protein expression, whereas MGMT protein expression was elevated when compared with untreated HCC rats. Thus, CALAF could be effective in protecting against DEN-induced HCC in rats by ameliorating hepatic injury and genotoxicity.
Literature
go back to reference Ahmad MS, Suardi N, Shukri A, Mohammad H, Oglat AA, Abunahel BM, Mohamed ABM, Makhamrah O (2019) Current status regarding tumour progression, surveillance, diagnosis, staging, and treatment of hcc: a literature review. J Gastroenterol Hepatol Res 8:2841–2852CrossRef Ahmad MS, Suardi N, Shukri A, Mohammad H, Oglat AA, Abunahel BM, Mohamed ABM, Makhamrah O (2019) Current status regarding tumour progression, surveillance, diagnosis, staging, and treatment of hcc: a literature review. J Gastroenterol Hepatol Res 8:2841–2852CrossRef
go back to reference Amereh Z, Hatami N, Shirazi F, Gholami S, Hosseini HS, Noubarani M, Kamalinejad M, Andalib S, Keyhanfar F, Eskandari RM (2017) Cancer chemoprevention by oleaster (Elaeagnus angustifoli L.) fruit extract in a model of hepatocellular carcinoma induced by diethylnitrosamine in rats. ExCLI J Sci 16:1046–1056 Amereh Z, Hatami N, Shirazi F, Gholami S, Hosseini HS, Noubarani M, Kamalinejad M, Andalib S, Keyhanfar F, Eskandari RM (2017) Cancer chemoprevention by oleaster (Elaeagnus angustifoli L.) fruit extract in a model of hepatocellular carcinoma induced by diethylnitrosamine in rats. ExCLI J Sci 16:1046–1056
go back to reference Anaga AO, Njoku CJ, Ekejuiba ES, Esiaka MN, Asuzu IU (2004) Investigations of the methanolic leaf extract of Costus afer Ker Gawl. for pharmacological activities in vitro and in vivo. Phytomed 11:242–248CrossRef Anaga AO, Njoku CJ, Ekejuiba ES, Esiaka MN, Asuzu IU (2004) Investigations of the methanolic leaf extract of Costus afer Ker Gawl. for pharmacological activities in vitro and in vivo. Phytomed 11:242–248CrossRef
go back to reference Anyakeme T, Essien ES, Akinnawor JO (2014) Hepatoprotective effect of methanolic stem extract of bush cane (Costus afer) on immunologic response generated reactive oxygen species (ROS) in alcohol-induced liver cirrhosis in rats. Asian J Biochem Pharm Res 4:215–223 Anyakeme T, Essien ES, Akinnawor JO (2014) Hepatoprotective effect of methanolic stem extract of bush cane (Costus afer) on immunologic response generated reactive oxygen species (ROS) in alcohol-induced liver cirrhosis in rats. Asian J Biochem Pharm Res 4:215–223
go back to reference Anyasor GN, Onajobi F, Osilesi O, Adebawo O (2014) Proximate composition, mineral content and in vitro antioxidant activity of leaf and stem of Costus afer (ginger lily). J Intercult Ethnopharmacol 3:128–134CrossRefPubMedPubMedCentral Anyasor GN, Onajobi F, Osilesi O, Adebawo O (2014) Proximate composition, mineral content and in vitro antioxidant activity of leaf and stem of Costus afer (ginger lily). J Intercult Ethnopharmacol 3:128–134CrossRefPubMedPubMedCentral
go back to reference Anyasor GN, Onajobi F, Osilesi O, Adebawo O, Oboutor E (2015) Evaluation of Costus afer Ker Gawl. in vitro anti-inflammatory activity and its chemical constituents identified using gas chromatography mass spectrometry analysis. J Coast Life Med 3:132–138 Anyasor GN, Onajobi F, Osilesi O, Adebawo O, Oboutor E (2015) Evaluation of Costus afer Ker Gawl. in vitro anti-inflammatory activity and its chemical constituents identified using gas chromatography mass spectrometry analysis. J Coast Life Med 3:132–138
go back to reference Aweke G (2007) Costus afer Ker Gawl. record from PROTA4U. Schmelzer GH & Gurib-Fakim A (Editors). PROTA (Plant Resources of Tropical Africa/Ressourcesvégétales de l’Afrique Tropicale), Wageningen, Netherlands. Retrieved December 16, 2019, from http://www.prota4u.org/search.asp. Aweke G (2007) Costus afer Ker Gawl. record from PROTA4U. Schmelzer GH & Gurib-Fakim A (Editors). PROTA (Plant Resources of Tropical Africa/Ressourcesvégétales de l’Afrique Tropicale), Wageningen, Netherlands. Retrieved December 16, 2019, from http://​www.​prota4u.​org/​search.​asp.
go back to reference Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Ann Biochem 239:70–76CrossRef Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Ann Biochem 239:70–76CrossRef
go back to reference Biselli M, Conti F, Gramenzi A, Frigerio M, Cucchetti A, Fatti G, D’Angelo M, Dall’Agata M, Giannini EG, Farinati F, Ciccarese F, Andreone P, Bernardi M, Trevisani F (2015) A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis. Br J Cancer 112:69–76CrossRefPubMed Biselli M, Conti F, Gramenzi A, Frigerio M, Cucchetti A, Fatti G, D’Angelo M, Dall’Agata M, Giannini EG, Farinati F, Ciccarese F, Andreone P, Bernardi M, Trevisani F (2015) A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis. Br J Cancer 112:69–76CrossRefPubMed
go back to reference Buetler E, Duran O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888 Buetler E, Duran O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
go back to reference Chou W-C, Lee C-N, Yang T-S, Huang C-Y, Teng W, Tseng Y-T, Chen J-S, Lin Y-C, Hou M-M, Chang HH, Hsieh JC-H (2018) Changes in serum α-fetoprotein level predicts treatment response and survival in hepatocellular carcinoma patients and literature review. J Formos Med Assoc 117(2):153–163CrossRefPubMed Chou W-C, Lee C-N, Yang T-S, Huang C-Y, Teng W, Tseng Y-T, Chen J-S, Lin Y-C, Hou M-M, Chang HH, Hsieh JC-H (2018) Changes in serum α-fetoprotein level predicts treatment response and survival in hepatocellular carcinoma patients and literature review. J Formos Med Assoc 117(2):153–163CrossRefPubMed
go back to reference Ebrahimzadeh MA, Nabavi SM, Nabavi SF, Bahramian F, Bekhradnia AR (2010) Antioxidant and free radical scavenging activity of H. officinalis, L. Var. angustifolius, V. odorata, B. hyrcana and C. speciosum. Pak J Pharm Sci 23:29–34PubMed Ebrahimzadeh MA, Nabavi SM, Nabavi SF, Bahramian F, Bekhradnia AR (2010) Antioxidant and free radical scavenging activity of H. officinalis, L. Var. angustifolius, V. odorata, B. hyrcana and C. speciosum. Pak J Pharm Sci 23:29–34PubMed
go back to reference El-Far AH, Badria FA, Shaheen HM (2016) Possible anticancer mechanisms of some Costus speciosus active ingredients concerning drug discovery. Curr Drug Discov Technol 13(3):123–143CrossRefPubMedPubMedCentral El-Far AH, Badria FA, Shaheen HM (2016) Possible anticancer mechanisms of some Costus speciosus active ingredients concerning drug discovery. Curr Drug Discov Technol 13(3):123–143CrossRefPubMedPubMedCentral
go back to reference Ezejiofor AN, Orisakwe OE (2017) Evaluation of protective effect of aqueous leave extract of Costus afer on female albino Wistar rats exposed to lead acetate. EC Pharmacol Toxicol 4:75–92 Ezejiofor AN, Orisakwe OE (2017) Evaluation of protective effect of aqueous leave extract of Costus afer on female albino Wistar rats exposed to lead acetate. EC Pharmacol Toxicol 4:75–92
go back to reference Ezejiofor AN, Orish CN, Orisakwe OE (2013) Effect of aqueous leaves extract of Costus afer Ker Gawl. (Zingiberaceae) on the liver and kidney of male albino Wistar rat. Anc Sci Life 33:4–9CrossRefPubMedPubMedCentral Ezejiofor AN, Orish CN, Orisakwe OE (2013) Effect of aqueous leaves extract of Costus afer Ker Gawl. (Zingiberaceae) on the liver and kidney of male albino Wistar rat. Anc Sci Life 33:4–9CrossRefPubMedPubMedCentral
go back to reference Fujiwara N, Friedman S, Goossens N, Hoshida Y (2017) Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 68:526–549CrossRefPubMedPubMedCentral Fujiwara N, Friedman S, Goossens N, Hoshida Y (2017) Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 68:526–549CrossRefPubMedPubMedCentral
go back to reference Hussain SP, Amstad P, Raja K, Ambs S, Nagashima M, Bennet WP, Shields PG, Ham AJ, Swenberg JA, Marrogi AJ, Harris CC (2000) Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res 60:3333–3337 Hussain SP, Amstad P, Raja K, Ambs S, Nagashima M, Bennet WP, Shields PG, Ham AJ, Swenberg JA, Marrogi AJ, Harris CC (2000) Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res 60:3333–3337
go back to reference Huang ZZ, Chen C, Zeng Z, Yang H, Oh H et al (2010) Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver generation. FASEB 15:19–21CrossRef Huang ZZ, Chen C, Zeng Z, Yang H, Oh H et al (2010) Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver generation. FASEB 15:19–21CrossRef
go back to reference Jacinto FV, Esteller M (2007) Mutator pathways unleashed by epigenetic silencing in human cancer. Mutagenesis 22:247–253CrossRefPubMed Jacinto FV, Esteller M (2007) Mutator pathways unleashed by epigenetic silencing in human cancer. Mutagenesis 22:247–253CrossRefPubMed
go back to reference Jahan MS, Vani G, Shyamaladevi CS (2011) Anticarcinogenic effect of Solarium trilobatum in diethylnitrosamine induced and phenobarbital promoted hepatocarcinogenesis in rats. Asian J Biochem 6(1):74–81CrossRef Jahan MS, Vani G, Shyamaladevi CS (2011) Anticarcinogenic effect of Solarium trilobatum in diethylnitrosamine induced and phenobarbital promoted hepatocarcinogenesis in rats. Asian J Biochem 6(1):74–81CrossRef
go back to reference Kaina B, Christmann M, Naumann S, Roos WP (2007) Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair 6:1079–1099CrossRefPubMed Kaina B, Christmann M, Naumann S, Roos WP (2007) Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair 6:1079–1099CrossRefPubMed
go back to reference Li F, Fernandez PP, Rajendra P, Hui KM, Sethi G (2010) Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells. Cancer Lett 292:197–207CrossRefPubMed Li F, Fernandez PP, Rajendra P, Hui KM, Sethi G (2010) Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells. Cancer Lett 292:197–207CrossRefPubMed
go back to reference Lin RC, Hanquet B, Mareh-Aleth L (1996) Aferoside A, a steroidal saponin from Costus afer. Phytochem 43:665–668CrossRef Lin RC, Hanquet B, Mareh-Aleth L (1996) Aferoside A, a steroidal saponin from Costus afer. Phytochem 43:665–668CrossRef
go back to reference Marengo B, Ciucis CD, Ricciarelli R, Romano P, Passalacquaet M et al (2010) DNA oxidative damage of neoplastic rat liver lesions. Oncol 23:1241–1246 Marengo B, Ciucis CD, Ricciarelli R, Romano P, Passalacquaet M et al (2010) DNA oxidative damage of neoplastic rat liver lesions. Oncol 23:1241–1246
go back to reference McCord JM, Fridovich I (1969) Superoxide dismutase: an enzyme function for erythrocuprein. J Biol Chem 244:6049–6055PubMed McCord JM, Fridovich I (1969) Superoxide dismutase: an enzyme function for erythrocuprein. J Biol Chem 244:6049–6055PubMed
go back to reference McCune LM, Johns T (2002) Antioxidant activity in medicinal plants associated with the symptoms of diabetes mellitus used by the indigenous peoples of the North American boreal forest. J Ethnopharmcol 82:197–205CrossRef McCune LM, Johns T (2002) Antioxidant activity in medicinal plants associated with the symptoms of diabetes mellitus used by the indigenous peoples of the North American boreal forest. J Ethnopharmcol 82:197–205CrossRef
go back to reference Mittal S, El-Serag HB (2013) Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 47:2–6CrossRef Mittal S, El-Serag HB (2013) Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 47:2–6CrossRef
go back to reference National Institutes of Health (2011) Guide for the Care and Use of Laboratory Animals, 8th edn. The National Academies Press, Washington DC National Institutes of Health (2011) Guide for the Care and Use of Laboratory Animals, 8th edn. The National Academies Press, Washington DC
go back to reference Organization for Economic Cooperation Development (2001) The OECD Guideline for Testing of Chemical. The Organization of Economic Co-operation Development, Paris Organization for Economic Cooperation Development (2001) The OECD Guideline for Testing of Chemical. The Organization of Economic Co-operation Development, Paris
go back to reference Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB, Ogunpolu BS, Daramola O (2015) Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environ Toxicol 30(11):1235–1243CrossRefPubMed Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB, Ogunpolu BS, Daramola O (2015) Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environ Toxicol 30(11):1235–1243CrossRefPubMed
go back to reference Prashant T, Bimlesh K, Mandeep K, Gurpreet K, Harleen K (2011) Phytochemical screening and extraction: a review. Int Pharm Sci 1:98–106 Prashant T, Bimlesh K, Mandeep K, Gurpreet K, Harleen K (2011) Phytochemical screening and extraction: a review. Int Pharm Sci 1:98–106
go back to reference Prieto RL, Pineda M, Aquilar M (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Ann Biochem 269:337–341CrossRef Prieto RL, Pineda M, Aquilar M (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Ann Biochem 269:337–341CrossRef
go back to reference Sasaki Y, Yamada T, Tanaka H, Ohigashi H, Eguchi H, Yano M, Ishikawa O, Imaoka S (2006) Risk of recurrence in a long term follow-up after surgery in 417 patients with hepatitis B or hepatitis C related hepatocellular carcinoma. Ann Surg 244:771–780CrossRefPubMedPubMedCentral Sasaki Y, Yamada T, Tanaka H, Ohigashi H, Eguchi H, Yano M, Ishikawa O, Imaoka S (2006) Risk of recurrence in a long term follow-up after surgery in 417 patients with hepatitis B or hepatitis C related hepatocellular carcinoma. Ann Surg 244:771–780CrossRefPubMedPubMedCentral
go back to reference Shiraishi A, Sakumi K, Sekihuchi M (2000) Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase. Carcinogenesis 21:1879–1883CrossRefPubMed Shiraishi A, Sakumi K, Sekihuchi M (2000) Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase. Carcinogenesis 21:1879–1883CrossRefPubMed
go back to reference Tcheghebe OT, Tala VR, Fouodjouo M (2018) Ethnobotanical uses, phytochemical and pharmacological profiles and toxicity of Costus afer ker Gawl. J Sci Res Allied Sci 4:1–11 Tcheghebe OT, Tala VR, Fouodjouo M (2018) Ethnobotanical uses, phytochemical and pharmacological profiles and toxicity of Costus afer ker Gawl. J Sci Res Allied Sci 4:1–11
go back to reference Vargas-Mendoza N, Madrigal-Santillan E, Morales-Gonzalez A, Esquivel-Soto J, Esquivel-Chirino C, Garcia Luna M, Gonzalez-Rubio MG, Gayosso-de-Lucio JA, Morales-Gonzalez JA (2014) Hepatoprotective effect of silymarin. World J Hepatol 6:144–149CrossRefPubMedPubMedCentral Vargas-Mendoza N, Madrigal-Santillan E, Morales-Gonzalez A, Esquivel-Soto J, Esquivel-Chirino C, Garcia Luna M, Gonzalez-Rubio MG, Gayosso-de-Lucio JA, Morales-Gonzalez JA (2014) Hepatoprotective effect of silymarin. World J Hepatol 6:144–149CrossRefPubMedPubMedCentral
go back to reference Veeraraghavan VP, Mohan SK, Jainu M, Seshadri C (2015) Ameliorating effects of Garcinia mangostana Linn pericarp extract on hepatic antioxidants in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC). Indian J Pharm Educ Res 49:344–352CrossRef Veeraraghavan VP, Mohan SK, Jainu M, Seshadri C (2015) Ameliorating effects of Garcinia mangostana Linn pericarp extract on hepatic antioxidants in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC). Indian J Pharm Educ Res 49:344–352CrossRef
go back to reference Verna L, Whysner J, Williams GM (1996) N-Nitrodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther 71:57–81CrossRefPubMed Verna L, Whysner J, Williams GM (1996) N-Nitrodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther 71:57–81CrossRefPubMed
go back to reference Xu JH, Chang WH, Fu HW, Yuan T, Chen P (2018) The mRNA, miRNA and lncRNA networks in hepatocellular carcinoma: an integrative transcriptomic analysis from gene expression omnibus. Mol Med Rep 17:6472–6482PubMedPubMedCentral Xu JH, Chang WH, Fu HW, Yuan T, Chen P (2018) The mRNA, miRNA and lncRNA networks in hepatocellular carcinoma: an integrative transcriptomic analysis from gene expression omnibus. Mol Med Rep 17:6472–6482PubMedPubMedCentral
Metadata
Title
Evaluation of the hepatoprotective effect of oral administration of aqueous fraction of methanolic extract of Costus afer leaves during induction of hepatocellular carcinoma with diethylnitrosamine in rats
Authors
Godswill N. Anyasor
Damilola P. Idowu
Williams Nabofa
Publication date
01-06-2020
Publisher
Springer London
Published in
Comparative Clinical Pathology / Issue 3/2020
Print ISSN: 1618-5641
Electronic ISSN: 1618-565X
DOI
https://doi.org/10.1007/s00580-020-03124-w

Other articles of this Issue 3/2020

Comparative Clinical Pathology 3/2020 Go to the issue