Crassocephalum rubens mitigates hepatic damage in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland toxicity in rats
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Abstract
Crassocephalum rubens has several medicinal properties, making it effective against several ailments, including its local use for treating liver problems and breast cancer. The effect of crude extract of Crassocephalum rubens (CECR) against liver damage in 7, 12 - dimethylbenz[a]anthracene (DMBA)-induced mammary gland toxicity was investigated in female Wistar rats. Rats were divided into group of 5 (n = 8). Group 1 served as control. Animals in groups 2 to 4 were administered a single intraperitoneal dose of DMBA at 20 mg/kg. Groups 3 and 4 rats were thereafter treated with 250 mg/kg and 500 mg/kg b.w CECR, respectively, for 12 weeks. Rats in group 5 were given 500 mg/kg b.w. CECR only for 12 weeks. Effect of CECR on DMBA-induced anomalies was investigated by using various biochemical parameters, including liver marker enzymes, oxidative stress, and tissue histology and cell count. CECR ameliorated the hepatic damage accompanied with DMBA-induced mammary gland toxicity by mitigating the abnormal changes noted in the levels of the parameters investigated. This could be proved by a significant (p<0.05) reduction in the levels of serum transaminases, dehydrogenase (LDH), gamma-glutamyl transferase (GGT), lactate malondialdehyde (MDA) and estrogen, and a significant (p<0.05) increase in the levels of superoxide dismutase (SOD) and liver cell count when compared with DMBA-intoxicated rats. The CECR, mostly at 500 mg/kg. b.w. dose, could serve as an alternative therapy against liver inflammation and oxidative stress associated with DMBA-induced mammary gland toxicity.
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Loha M, Mulu A, Abay SM, Ergete W, Geleta B. Acute and Subacute Toxicity of Methanol Extract of Syzygium guineense Leaves on the Histology of the Liver and Kidney and Biochemical Compositions of Blood in Rats. Evid Based Complement Alternat Med. 2019; 2019:5702159. doi:10.1155/2019/5702159
Aghoutane B, Naama A, Attar IE, El-Gourrami O, Monfalouti HE, Kartah BE. Phytochemical Composition, Antibacterial Activity and Acute Toxicity Studies of Euphorbia resinifiera O. Berg. Trop J Nat Prod Res. 2024; 8(4):6814-9. doi:10.26538/tjnpr/v8i4.10
Adewale OB, Anadozie SO, Potts-Johnson SS, Onwuelu JO, Obafemi TO, Osukoya OA, Fadaka AO, Davids H, Roux S. Investigation of bioactive compounds in Crassocephalum rubens leaf and in vitro anticancer activity of its biosynthesized gold nanoparticles. Biotechnol Rep. 2020:e00560. doi:https://doi.org/10.1016/j.btre.2020.e00560
Alhassan SO, Atawodi SE-O. Chemopreventive effect of dietary inclusion with Crassocephalum rubens (Juss ex Jacq) leaf on N-methyl-N-nitrosourea (MNU)-induced colorectal carcinogenesis in Wistar rats. J Funct Foods. 2019; 63:103589. doi:https://doi.org/10.1016/j.jff.2019.103589
Hanamornroongruang S, Sangchay N. Acute liver failure associated with diffuse liver infiltration by metastatic breast carcinoma: A case report. Oncol Lett. 2013; 5(4):1250-2. doi:10.3892/ol.2013.1165
Wendon J, Cordoba J, Dhawan A, Larsen FS, Manns M, Samuel D, Simpson KJ, Yaron I, Bernardi M. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017; 66(5):1047-81. doi:10.1016/j.jhep.2016.12.003
Ashrafi M, Karimi B, Sabahi M, Shomali T. Hepatoprotective effect of simvastatin in mice with DMBA-induced breast cancer: Histopathological, biochemical and antioxidant status evaluation. Biomed Res Ther. 2018; 5:2064-77. doi:10.15419/bmrat.v5i3.421
Rai N, Kailashiya V, Gautam V. Exploring the Protective Effect against 7,12-Dimethylbenz[a]anthracene-Induced Breast Tumors of Palmitoylethanolamide. ACS Pharmacol Transl Sci. 2024; 7(1):97-109. doi:10.1021/acsptsci.3c00188
Adewale OB, Egbeyemi KA, Onwuelu JO, Potts-Johnson SS, Anadozie SO, Fadaka AO, Osukoya OA, Aluko BT, Johnson J, Obafemi TO, Onasanya A. Biological synthesis of gold and silver nanoparticles using leaf extracts of Crassocephalum rubens and their comparative in vitro antioxidant activities. Heliyon. 2020; 6(11):e05501. doi:https://doi.org/10.1016/j.heliyon.2020.e05501
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957; 28(1):56-63. doi:http://www.ncbi.nlm.nih.gov/pubmed/13458125
Szasz G. A Kinetic Photometric Method for Serum γ-Glutamyl Transpeptidase. Clin Chem. 1969; 15(2):124-36. doi:10.1093/clinchem/15.2.124
Weisshaar D, Gossrau E, Faderl B. [Normal ranges of alpha-HBDH, LDH, AP, and LAP as measured with substrate-optimated test charges]. 1975; 26(9):387-92.
McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). 1969; 244(22):6049-55.
Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52:302-10. doi:10.1016/s0076-6879(78)52032-6
Evbuomwan IO, Stephen Adeyemi O, Oluba OM. Indigenous medicinal plants used in folk medicine for malaria treatment in Kwara State, Nigeria: an ethnobotanical study. BMC Complement Med Ther. 2023; 23(1):324. doi:10.1186/s12906-023-04131-4
Sibuyi NRS, Thipe VC, Panjtan-Amiri K, Meyer M, Katti KV. Green synthesis of gold nanoparticles using Acai berry and Elderberry extracts and investigation of their effect on prostate and pancreatic cancer cells. Nanobiomedicine. 2021; 8:1849543521995310. doi:10.1177/1849543521995310
Adjatin A, Dansi A, Badoussi E, Loko Y, Dansi M, Gbaguidi F, Azokpota P, Ahissou H, Akoègninou A, Akpagana K. Phytochemical screening and toxicity studies of Crassocephalum rubens (Juss. ex Jacq.) S. Moore and Crassocephalum crepidioides (Benth.) S. Moore consumed as vegetable in Benin. J Chem Pharm Res. 2013; 5(6):160-7.
N’guessan BB, Asiamah AD, Arthur NK, Frimpong-Manso S, Amoateng P, Amponsah SK, Kukuia KE, Sarkodie JA, Opuni KF-M, Asiedu-Gyekye IJ, Appiah-Opong R. Ethanolic extract of Nymphaea lotus L. (Nymphaeaceae) leaves exhibits in vitro antioxidant, in vivo anti-inflammatory and cytotoxic activities on Jurkat and MCF-7 cancer cell lines. BMC Complement Med Ther. 2021; 21(1):22. doi:10.1186/s12906-020-03195-w
Husni E, Dillasamola D, Jannah M. Subacute Toxicity Test of Ethanol Extract of Sungkai Leaf (Peronema Canescens Jack.) on Sgot and Sgpt Levels. Trop J Nat Prod Res. 2023; 7(11):5046-9.
Avtandilyan N, Javrushyan H, Mamikonyan A, Grigoryan A, Trchounian A. The potential therapeutic effect of N(G)-hydroxy-nor-L-arginine in 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats. Exp Mol Pathol. 2019; 111:104316. doi:10.1016/j.yexmp.2019.104316
Nassan MA, Soliman MM, Ismail SA, El-Shazly S. Effect of Taraxacum officinale extract on PI3K/Akt pathway in DMBA-induced breast cancer in albino rats. Biosci Rep. 2018; 38(6):BSR20180334. doi:10.1042/BSR20180334
Hamza AA, Khasawneh MA, Elwy HM, Hassanin SO, Elhabal SF, Fawzi NM. Salvadora persica attenuates DMBA-induced mammary cancer through downregulation oxidative stress, estrogen receptor expression and proliferation and augmenting apoptosis. Biomed Pharmacother. 2022; 147:112666. doi:https://doi.org/10.1016/j.biopha.2022.112666
Arora R, Bhushan S, Kumar R, Mannan R, Kaur P, Singh AP, Singh B, Vig AP, Sharma D, Arora S. Hepatic dysfunction induced by 7, 12-dimethylbenz(α)anthracene and its obviation with erucin using enzymatic and histological changes as indicators. Plos One. 2014; 9(11):e112614-e. doi:10.1371/journal.pone.0112614
Anbalagan V, Raju K, Shanmugam M. Assessment of Lipid Peroxidation and Antioxidant Status in Vanillic Acid Treated 7,12-Dimethylbenz[a]anthracene Induced Hamster Buccal Pouch Carcinogenesis. J Clin Diagn Res. 2017; 11(3):BF01-BF4. doi:10.7860/JCDR/2017/23537.9369
Abou Seif HS. Physiological changes due to hepatotoxicity and the protective role of some medicinal plants. Beni Suef Univ J Basic Appl Sci. 2016; 5(2):134-46. doi:10.1016/j.bjbas.2016.03.004
Wang Z, Zhang X. Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats. Front Pharmacol. 2017; 8:320-. doi:10.3389/fphar.2017.00320
Hussain S, Ashafaq M, Alshahrani S, Bokar IAM, Siddiqui R, Alam MI, Taha MME, Almoshari Y, Alqahtani SS, Ahmed RA, Jali AM, Qadri M. Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats. Molecules. 2023; 28(2). doi:10.3390/molecules28020881
Ma Z, Kim YM, Howard EW, Feng X, Kosanke SD, Yang S, Jiang Y, Parris AB, Cao X, Li S, Yang X. DMBA promotes ErbB2‑mediated carcinogenesis via ErbB2 and estrogen receptor pathway activation and genomic instability. Oncol Rep. 2018; 40(3):1632-40. doi:10.3892/or.2018.6545
Kubatka P, Uramova S, Kello M, Kajo K, Samec M, Jasek K, Vybohova D, Liskova A, Mojzis J, Adamkov M, Zubor P, Smejkal K, Svajdlenka E, Solar P, Samuel SM, Zulli A, Kassayova M, Lasabova Z, Kwon TK, Pec M, Danko J, Büsselberg D. Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma In Vivo and In Vitro. Int J Mol Sci. 2019; 20(7):1749. doi:https://www.mdpi.com/1422-0067/20/7/1749
Patil RA, Lokwani PS, Amrutkar SV. Phytochemical Evaluation and Antihypertensive Activity of Malus domestica Peel in Experimental Animals. Pharmacophore. 2022; 13(3):1–7.
Kumarappan C, Mandal SC. Short Communication Polyphenol extract of Ichnocarpus frutescens leaves modifies hyperglycemia in dexamethasone (dex) treated rats. Indian J Physiol Pharmacoly. 2014; 58(1):441–5.
Shittu STT, Lasisi TJ, Shittu SAS, Adeyemi A, Adeoye TJ, Alada AA. Ocimum gratissimum enhances insulin sensitivity in male Wistar rats with dexamethasone-induced insulin resistance. J Diabetes Metab Disord. 2021; 20(2):1257–67.
Wego MT, Poualeu Kamani SL, Miaffo D, Nchouwet ML, Kamanyi A, Wansi Ngnokam SL. Protective Effects of Aqueous Extract of Baillonella toxisperma Stem Bark on Dexamethasone-Induced Insulin Resistance in Rats. Adv Pharmacol Sci. 2019; 2019:1–6.
Dzinyela R, Asomaning E, Abdul Nasir A, Alhassan A, Movahedi, A. An in vivo Evaluation of Antihyperlipidaemic Activity of Ethanolic Extract of Amaranthus spinosus Leaves on Dexamethasone Induced Hyperlipidaemic Rats. Biochem Mol Bio. 2021; 6: 25-34. 10.11648/j.bmb.20210602.12.
Sholapur H, Patil B. Effect of Moringa oleifera Bark Extracts on Dexamethasone-induced Insulin Resistance in Rats. Drug Res. 2013; 63(10):527–31.
Mahamad AT, Miaffo D, Poualeu Kamani SL, Mahamat O, Kamanyi A, Wansi Ngnokam SL. Glucose, lipid and oxidative stress lowering activity of the aqueous extract from leafy stems of Cissus polyantha Gilg & Brandt in dexamethasone-induced hyperglycemia in rats. J Diabetes Metab Disord. 2020; 19(2):1527–35.
Munna S, Saleem MTS. Hypoglycemic and hypolipidemic activity of Ficus mollis leaves. Rev Bra Farmacog. 2013;23(4):687–91.
Fofié CK, Nguelefack-Mbuyo EP, Tsabang N, Kamanyi A, Nguelefack TB. Hypoglycemic Properties of the Aqueous Extract from the Stem Bark of Ceiba pentandra in Dexamethasone-Induced Insulin Resistant Rats. Evid Based Complement Alternat Med. 2018; 2018:1–11.
Yegdaneh A, Safaeian L, Halvaei-Varnousfaderani M, Bazvand S. Antihyperlipidemic and antioxidant effects of ethanol fraction of Sargassum angustifolium in dexamethasone-induced dyslipidemic rats. Res J Pharmacog. 2022; 9(1):39–49.
Poualeu Kamani S, Kamgaing Waguia J, Miaffo D, Nchouwet M, Demeni Kadji C, Wego Kamgaing MT, Douho Djimeli R, Mzoyem Ngnitedem J, Kamanyi A, Wansi Ngnokam S. Efficacy of Emilia coccinea aqueous extract on inhibition of α-amylase enzyme activity and insulin resistance in dexamethasone treated-rats. Metabol Open. 2022; 15:100193.
Tamboli AM, Karpe ST, Shaikh SA, Manikrao AM, Kature DV. Hypoglycemic activity of extracts of Oroxylum indicum (L.) vent roots in animal models. Pharmacol (online). 2011; 2:890–9.
Okwuosa CN, Unekwe PC, Achukwu PU, Udeani TKC, Ogidi UH. Glucose and triglyceride lowering activity of Pterocarpus santaniloides leaf extracts against dexamethasone induced hyperlipidemia and insulin resistance in rats. Afr J Biotechnol. 2011; 10(46):9415–20.
Das S, Baruah M, Shill D. Evaluation of antidiabetic activity from the stem of Lasia spinosa in dexamethasone induced diabetic albino rats. J Pharm Chem Biol Sci. 2014; 1(1):12–7.
Shil D, Mohanty JP, Saleem T, Uriah T. Anti-Diabetic Activity of Leaf Extract of Nepenthes khasiana Hook on Dexamethasone Induced Diabetic Rats. J Pharm Chem Biol Sci. 2014; 1(1):6–11.
Sholapur HN, Patil BM. Effect of Fractions of Alcoholic Extract of Moringa oleifera Lam. Bark on Dexamethasone 46.induced Insulin Resistance in Rats. J Young Pharm. 2017; 9(3):410–6.
Builders MI, Joseph OS, Vhriterhire AR. Effect of Parkia biglobosa extract on open skin wound healing in dexamethasone- induced hyperglycaemia and histological assessment in rats. Afr J Pharm Pharmacol. 2019;13(8):84–9.
Safaeian L, Zolfaghari B, Assarzadeh N, Ghadirkhomi A. Antioxidant and Anti-hyperlipidemic Effects of Bark Extract of Pinus eldarica in Dexamethasone-induced Dyslipidemic Rats. J Adv Med Biomed Res. 2019; 27(125):49–56.
Miaffo D, Ntchapda F, Poualeu Kamani SL, Kopodjing Bello A, Mahamad TA, Maidadi B, Kolefer K. Tapinanthus dodoneifolius leaf inhibits the activity of carbohydrate digesting enzymes and improves the insulin resistance induced in rats by dexamethasone. Metabol Open. 2023; 18:100238.
Sadeghi Dinani M, Safaeian L, Mohsen M, Mohammadzamani Y. Allium affine extract improves dexamethasone-induced hyperlipidemia in rats. Res J Pharmacog. 2023; 10(2):9–17.
Reddy NVS, Aveti S, Anjum M, Raju GM. Anti-Hyperlipidemic Activity of Methanolic Extract of Syzygium Alternifolium Bark Against High-Fat Diet And Dexamethasone-Induced Hyperlipidemia In Rats. Asian J Pharm Clin Res. 2015; 8(6):165-168
Shil D, Mohanty JP, Das T, Bhuyan NR, Uriah T, Uriah T. Protective role of pitcher of Nepenthes khasiana hook against dexamethazone induced hyperlipidemia and insulin resistance in rats. Int J Res Pharm Sci. 2010; 1(2):195-198.
Aru M, Alev K, Pehme A, Purge P, Õnnik L, Ellam A, Kaasik P, Seene T. Changes in Body Composition of Old Rats at Different Time Points After Dexamethasone Administration. Curr Aging Sci. 2019; 11(4):255–60.
Jahng JW, Kim NY, Ryu V, Yoo SB, Kim BT, Kang DW, Lee JH. Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats. Eur J Pharmacol. 2008; 581(1–2):64–70.
Eckland DJA, Harbuz MS, Jessop DS, Lightman SL. Corticotrophin-releasing factor and arginine vasopressin in the hypothalamo-hypophyseal portal blood of rats following high-dose glucocorticoid treatment and withdrawal. Brain Res. 1991; 568(1–2):311–3.
Erkut ZA, Pool C, Swaab DF. Glucocorticoids Suppress Corticotropin-Releasing Hormone and Vasopressin Expression in Human Hypothalamic Neurons. J Clin Endocrinol Metab. 1998; 83(6):2066–73.
Fink G, Robinson IC, Tannahill LA. Effects of adrenalectomy and glucocorticoids on the peptides CRF‐41, AVP and oxytocin in rat hypophysial portal blood. J Physiol. 1988; 401(1):329–45.
Young EA, Kwak SP, Kottak J. Negative Feedback Regulation following Administration of Chronic Exogenous Corticosterone. J Neuroendocrinol. 1995; 7(1):37–45.
Li X, Zheng L, Zhang B, Deng ZY, Luo T. The Structure Basis of Phytochemicals as Metabolic Signals for Combating Obesity. Front Nutr. 2022; 9:913883. doi: 10.3389/fnut.2022.913883.
Francini-Pesenti F, Spinella P, Calò LA. Potential role of phytochemicals in metabolic syndrome prevention and therapy. Diabetes Metab Syndr Obes. 2019; 12:1987–2002.
Liu K, Luo M, Wei S. The Bioprotective Effects of Polyphenols on Metabolic Syndrome against Oxidative Stress: Evidences and Perspectives. Oxid Med Cell Longev. 2019; 2019:1–16.
Jungbauer A, Medjakovic S. Phytoestrogens and the metabolic syndrome. J Steroid Biochem Mol Biol. 2014; 139:277–89.
Pasternak JJ, McGregor DG, Lanier WL. Effect of Single-Dose Dexamethasone on Blood Glucose Concentration in Patients Undergoing Craniotomy. J Neurosurg Anesthesiol. 2004; 16(2):122–5.
Martínez BB, Pereira ACC, Muzetti JH, Telles F de P, Mundim FGL, Teixeira MA. Experimental model of glucocorticoid-induced insulin resistance. Acta Cir Bras. 2016; 31(10):645–9.
Burén J, Liu H, Jensen J, Eriksson J. Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase B in primary cultured rat adipocytes. Eur J Endocrinol. 2002; 146(3): 419–29.
Nicod N, Giusti V, Besse C, Tappy L. Metabolic Adaptations to Dexamethasone‐Induced Insulin Resistance in Healthy Volunteers. Obes Res. 2003; 11(5):625–31.
Severino C, Brizzi P, Solinas A, Secchi G, Maioli M, Tonolo G. Low-dose dexamethasone in the rat: a model to study insulin resistance. Am J Physiol Endocrinol Metab. 2002; 283(2):E367–73.