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Chenopodium quinoa ethanolic extract ameliorates cyclophosphamide®-induced hepatotoxicity in male rats

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Abstract

Cancer is a disease that is associated with abnormal proliferation and growth of living cells, and cyclophosphamide® therapy results in hepatotoxicity. This study aimed to investigate ameliorative effect of Chenopodium quinoa ethanolic extract (QEE) against cyclophosphamide®-induced hepatotoxicity. Four groups (10 male Wistar rats each) were used: (1) healthy control group; (2) rats treated orally with QEE (400 mg/kg/day) for 4 weeks; (3) rats injected intraperitoneally with cyclophosphamide® (150 mg/kg/week) for 4 weeks; (4) rats received QEE after cyclophosphamide® intoxication another 4 weeks. The results revealed that QEE succeeded to decrease the hepatotoxicity-induced by cyclophosphamide®; this was evidenced by the significant reduction in serum ALAT, ASAT, GGT, ALP, total cholesterol, triglycerides, LDL-cholesterol, and TNF-α IL 1β and IL6, as well as hepatic MDA, nitric oxide levels, and DNA fragmentation coupled with a marked rise in serum albumin and HDL-cholesterol level as well as hepatic GSH, SOD, GPx, and catalase values. QEE succeeded also in improving the histopathological picture of the liver. It could be concluded that QEE succeeded, to a great extent, to counteract the oxidative stress and regenerated the liver against cyclophosphamide®-resultant hepatotoxicity. QEE could be considered a promising candidate as a food supplement for the protection against the side effects of cyclophosphamide®.

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References

  • Abdel-Wahhab KG, Mannaa FA, Ashry M, Mustafa MA, Fawzi H, Hassan LK (2019) Quinoa (Chenopodiumquinoa) extract ameliorates hemato-cardio injuries induced by cyclophosphamide®in rats. JIPBS 6(4):23–32

    CAS  Google Scholar 

  • Adikwu E, Bokolo B (2018) Effect of cimetidine on cyclophosphamide-induced liver toxicity in albino rats. Asian J Med Sci 9:50–56

    Google Scholar 

  • Ahmed RA (2018) Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide. J Basic Appl Zool 79:8

    Google Scholar 

  • Akay H, Akay T, Secilmis S, Kocak Z, Donderici O (2006) Hepatotoxicity after low-dose cyclophosphamide therapy. South Med J 99:1399–1400

    PubMed  Google Scholar 

  • Akcay A, Nguyen Q, Edelstein CL (2009) Mediators of inflammation in acute kidney injury. Mediat Inflamm 2009:137072

    Google Scholar 

  • Anand P, Kunnumakkara AB, Kunnumakara AB, Sundaram C, Arikumar KB, Tharakan ST et al (2008) Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 25(9):2097–2116

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arumugam N, Sivakumar V, Thanislass J, Devaraj H (1997) Effects of acrolein on rat liver antioxidant defense system. Indian J Exp Biol 35(12):1373–1374

    CAS  PubMed  Google Scholar 

  • Bhargava A, Shukla S, Ohri D (2006) Chenopodium quinoaan an Indian perspective. Ind Crop Prod 23(1):73–87

    CAS  Google Scholar 

  • Bhatia K, Ahmad F, Rashid H, Raisuddin S (2008) Protective effect of S-allylcysteine against cyclophosphamide-induced bladder hemorrhagic cystitis in mice. Food Chem Toxicol 46:3368–3374

    CAS  PubMed  Google Scholar 

  • Bowry VW, Stanley KK, Stocker R (1992) High density lipoprotein is the major of lipid hydroperoxides in human blood plasma from fasting donors. Proc Natl Acad Sci 89:1316–1320

    Google Scholar 

  • Circu ML, Aw TY (2011) Redox biology of the intestine. Free Radic Res 45:1245–1266

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dang K, Lamb K, Cohen M, Bielefeldt K, Gebhart GF (2008) Cyclophosphamide-induced bladder inflammation sensitizes and enhances P2X receptor function in rat bladder sensory neurons. J Neurophysiol 99:49–45

    CAS  PubMed  Google Scholar 

  • De Jonge ME, Huitema AD, Holtkamp MJ et al (2005) Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism. Cancer Chemother Pharmacol 56:370–378

    PubMed  Google Scholar 

  • Del Hierro JN, Herrera T, García-Risco MR, Fornari T, Reglero G, Martin D (2018) Ultrasound-assisted extraction and bioaccessibility of saponins from edible seeds: Quinoa, lentil, fenugreek, soybean and lupin. Food Res Int. Food Res Int 109:440–447

  • Drury RAB, Wallington EA (1980) Preparation and fixation of tissues. In: RAB D, Wallington EA (eds) Carleton’s histological technique. 5. Oxford University Press, Oxford, pp 41–54

    Google Scholar 

  • El-Halawany AM, Salah El Dine R, El Sayed NS, Hattori M (2014) Protective effect of Aframomum melegueta phenolics against CCl4-induced rat hepatocytes damage; role of apoptosis and pro-inflammatory cytokines inhibition. Sci Rep 4:5880

    PubMed  PubMed Central  Google Scholar 

  • Emadi A, Jones RJ, Brodsky RA (2009) Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol 6:638–647

    CAS  PubMed  Google Scholar 

  • Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI (2007) The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem 113:234–258

    CAS  PubMed  Google Scholar 

  • Fuentes F, Paredes-Gonzalez X (2013) The state of the world’s quinoa. Nutraceutical perspectives of quinoa: biological properties and functional applications. Rome: In FAO & CIRAD. State of the Art Report on Quinoa Around the World in; 2015, pp 286–99

  • Gould SF, Powell D, Nett T, Glod LM (1983) A rat model for chemotherapy-induced male infertility. Arch Androl 11:141–I50

    CAS  PubMed  Google Scholar 

  • Habeeb AA (2018) Moringa oleifera leaf extract: a potent ameliorator of cyclophosphamide induced liver toxicity in rat model. J Biosci Appl Res 4(1):22–38

    Google Scholar 

  • Hales BF (1982) Comparison of the mutagenicity and teratogenicity of cyclophosphamide and its active metabolites, 4-hydroxycyclophosphamide, phosphoramide mustard, and acrolein. Cancer Res 42(8):3016–3021

    CAS  PubMed  Google Scholar 

  • Hong YH, Huang YL, Liu YC, Tsai PJ (2016) Djulis (Chenopodium formosanum Koidz.) water extract and its bioactive components ameliorate dermal damage in UVB-irradiated skin models. Biomed Res Int 2016:7368797

  • Ishida Y, Kondo T, Ohshima T, Fujiwara H, Iwakura Y, Mukaida N (2002) A pivotal involvement of IFN-c in the pathogenesis of acetaminophen-induced acute liver injury. FASEB J 16:1227–1236

    CAS  PubMed  Google Scholar 

  • Jabir NR, Tabrez S, Ashraf GM, Shakil S, Damanhouri GA, Kamal MA (2012) Nanotechnology-based approaches in anticancer research. Int J Nanomed 7:4391–4408

    CAS  Google Scholar 

  • Jancurová M, Minarovicová L, Dandar A (2009) Quinoa–a review. Czech J Food Sci 27:71–79

    Google Scholar 

  • Jayaprakasha GK, Selvi T, Sakariah KK (2003) Antibacterial and antioxidant activities of grape (Vitis vinifera) seed extracts. Food Res Int 36(2):117–122

    CAS  Google Scholar 

  • Kern JC, Kehrer JP (2002) Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact 139(1):79–95

    CAS  PubMed  Google Scholar 

  • Kim SH, Lee IC, Ko JW, Moon C, Kim SH, Shin IS, Seo YW, Kim HC, Kim JC (2015) Diallyl disulfide prevents cyclophosphamide-induced hemorrhagic cystitis in rats through the inhibition of oxidative damage, MAPKs, and NF-κB pathways. Biomol Ther 23(2):180–188

    CAS  Google Scholar 

  • Kuljanabhagavad T, Thongphasuk P, Chamulitrat W, Wink M (2008) Triterpene saponins from Chenopodium quinoa Willd. Phytochem 69:1919–1926

    CAS  Google Scholar 

  • Laus MN, Cataldi MP, Robbe C, D’Ambrosio T, Amodio ML, Colelli G et al (2017) Antioxidant capacity, phenolic and vitamin C contents of quinoa (Chenopodium quinoa Willd.) as affected by sprouting and storage conditions. Ital J Agron 12:816

    Google Scholar 

  • Ledesma BH (2019) Quinoa (Chenopodium quinoa Willd.) as a source of nutrients and bioactive compounds: a review. Bioactive Compounds Health Dis 2(3):27–47

    Google Scholar 

  • Lixin X, Lijun Y, Songping H (2019) Ganoderic acid A against cyclophosphamide-induced hepatic toxicity in mice. J Biochem Mol Toxicol 33:e22271

    PubMed  Google Scholar 

  • Magalska A, Brzezinska A, Zmijewska AB, Piwocka GM, Sikora E (2006) Curcumin induces cell death without oligonucleosomal DNA fragmentation in quiescent and proliferating human CD8+ cells. Acta Biochim Pol 53:531–538

    CAS  PubMed  Google Scholar 

  • Mahmoud AM (2014) Hesperidin protects against cyclophosphamideinduced hepatotoxicity by upregulation of PPARc and abrogation of oxidative stress and inflammation. Can J Physiol Pharmacol 92:717–724

    CAS  PubMed  Google Scholar 

  • Mahmoud AM, Al Dera HS (2015) 18b-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARc and Nrf2 upregulation. Genes Nutr 10:41

    PubMed  PubMed Central  Google Scholar 

  • Mansour DF, Salama AA, Hegazy RR, Omara EA, Nada SA (2017) Whey protein isolate protects against cyclophosphamide-induced acute liver and kidney damage in rats. J Appl Pharm Sci 7(06):111–120

    CAS  Google Scholar 

  • Martınez-Gabarrón M, Enríquez R, Sirvent AE, García-Sepulcre M, Millán I, Amorós F (2011) Hepatotoxicity following cyclophosphamide treatment in a patient with MPO-ANCA vasculitis. Nefrologia 31:496–498

    PubMed  Google Scholar 

  • Matata BM, Galinanes M (2002) Peroxynitrite is an essential component of cytokines production mechanism in human monocytes through modulation of nuclear factor-kappa B DNA binding activity. J Biol Chem 277:2330–2335

    CAS  PubMed  Google Scholar 

  • McKim SE, Gäbele E, Isayama F et al (2003) Inducible nitric oxide synthase is required in alcohol-induced liver injury: studies with knockout mice. Gastroenterology 125:1834–1844

    CAS  PubMed  Google Scholar 

  • Mohammed NA, Abd El-Aleem SA, El-Hafiz HA, McMahon RF (2004) Distribution of constitutive (COX-1) and inducible (COX-2) cyclooxygenase in postviral human liver cirrhosis: a possible role for COX-2 in the pathogenesis of liver cirrhosis. J Clin Pathol 57:350–354

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mukhopadhyay P, Rajesh M, Horvath B, Batkai S, Park O, Tanchian G et al (2011) Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic Biol Med 50:1368–1381

    CAS  PubMed  PubMed Central  Google Scholar 

  • Muratori L, Ferrari R, Muratori P, Granito A, Bianchi FB (2005) Acute icteric hepatitis induced by a short course of low-dose cyclophosphamide in a patient with lupus nephritis. Dig Dis Sci 50(12):2364–2365

    PubMed  Google Scholar 

  • Nogala-Kalucka M, Korczak J, Dratwia M, Lampart-szczapa E, Siger A, Buchowski M (2005) Changes in antioxidant activity and free radical scavenging potential of rosemary extract and tocopherols in isolated rapeseed oil triacylglycerols during accelerated tests. Food Chem 93:227–235

    CAS  Google Scholar 

  • Oyagbemi AA, Omobowale OT, Asenuga ER, Akinleye AS, Ogunsanwo RO, Saba AB (2016) Cyclophosphamideinduced hepatotoxicity in Wistar rats: the modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical. Int J Prev Med 05:176.102.233.170

    Google Scholar 

  • Pasko P, Barton H, Zagrodzki P, Izewska A, Krosniak M, Gawlik M, Gawlik M, Gorinstein S (2010) Effect of diet supplemented with quinoa seeds on oxidative status in plasma and selected tissues of high fructose-fed rats. Plant Foods Hum Nutr 65(2):146–151

    CAS  PubMed  Google Scholar 

  • Perandones CE, Illera VA, Peckham D, Stunz LL, Ashman RF (1993) Regulation of apoptosis in vitro in mature murine spleen T cells. J Immunol 151(7):3521–3529

    CAS  PubMed  Google Scholar 

  • Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-jB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466

    CAS  PubMed  Google Scholar 

  • Ramaiah SK (2007) A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters. Food Chem Toxicol 45:1551–1557

    CAS  PubMed  Google Scholar 

  • Reiter R, Tang L, Garcia JJ, Munoz-Hoyos A (1997) Pharmacological actions of melatonin in oxygen radical pathophysiology. Life Sci 60(25):2255–2271

    CAS  PubMed  Google Scholar 

  • Ruales J, Nair BM (1992) Nutritional quality of the protein in quinoa (Chenopodium quinoa, Willd) seeds. Plant Foods Hum Nutr 42:1–11

    CAS  PubMed  Google Scholar 

  • Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron- induced lipid peroxidation of rat liver mi- crosomes. Steroids. 59:383–388

    CAS  PubMed  Google Scholar 

  • Saxen S, Shahani L, Bhatanagar P (2017) Hepatoprotective effect of Chenopodium quinoa seed against CCL4-induced liver toxicity in Swiss albino male mice. Asian J Pharm Clin Res 10(11):273–276

    Google Scholar 

  • Sethiya NK, Trivedi A, Mishra S (2014) The total antioxidant content and radical scavenging investigation on 17 phytochemical from dietary plant sources used globally as functional food. Biomed Prev Nutr 4:439–444. https://doi.org/10.1016/j.bionut.2014.03.007

    Article  Google Scholar 

  • Shokrzadeh M, Ahmadi A, Chabra A, Naghshvar F, Salehi F, Habibi E, Haghi-Aminjan H (2014) An ethanolic extract of Origanum vulgare attenuates cyclophosphamide-induced pulmonary injury and oxidative lung damage in mice. Pharm Biol 52:1229–1236. https://doi.org/10.3109/13880209.2013.879908

    Article  PubMed  Google Scholar 

  • Singh KV, Singh R (2016) Quinoa (Chenopodium quinoa Willd), functional superfood for today’s world: a review. World Sci News 58:84–96

    CAS  Google Scholar 

  • Srivastava A, Shivanandappa T (2010) Hepatoprotective effect of the root extract of Decalepis hamiltonii against carbon tetrachlorideinduced oxidative stress in rats. Food Chem 118:411–417

    CAS  Google Scholar 

  • Stankiewicz A, Skrzydlewska E, Makieła M (2002) Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats. Drug Metabol Drug Interact 19(2):67–82

    CAS  PubMed  Google Scholar 

  • Tacke F, Luedde T, Trautwein C (2009) Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol 36:4–12

    CAS  PubMed  Google Scholar 

  • Tripathi DN, Jena GB (2009) Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact 180:398–406

    CAS  PubMed  Google Scholar 

  • Waller RA, Duncan DB (1969) A Bayes rule for the symmetric multiple com-parisons problem. J Am Stat Assoc 64:1484–1503

    Google Scholar 

  • Wei XJ, Hu TJ, Chen JR, Wei YY (2011) Inhibitory effect of carboxymethylpachymaran on cyclophosphamide-induced oxidative stress in mice. Int J Biol Macromol 49:801–805

    CAS  PubMed  Google Scholar 

  • Xu G, McLeod HL (2001) Strategies for enzyme/prodrug cancer therapy. Clin Cancer Res 7:3314–3324

    CAS  PubMed  Google Scholar 

  • Yousefipour Z, Ranganna K, Newaz MA, Milton SG (2005) Mechanism of acrolein-induced vascular toxicity. J Physiol Pharmacol 56:337–353

    CAS  PubMed  Google Scholar 

  • Zhao G, Rodriguez BL (2013) Molecular targeting of liposomal anoparticles to tumor microenvironment. Int J Nanomed 8:61–71

    Google Scholar 

  • Zhao L, Zhang N, Yang D, Yang M, Guo X, He J, Wu W, Ji B, Cheng Q, Zhou F (2018) Protective effects of five structurally diverse flavonoid subgroups against chronic alcohol-induced hepatic damage in a mouse model. Nutrients 10:11

    Google Scholar 

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Correspondence to Khaled G. Abdel-Wahhab.

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All animals received human care in accordance with the standard institutional criteria for the care and use of experimental animals according to the Ethical Committee of the National Research Center (FWA 00014747).

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Abdel-Wahhab, K.G., Mannaa, F.A., Ashry, M. et al. Chenopodium quinoa ethanolic extract ameliorates cyclophosphamide®-induced hepatotoxicity in male rats. Comp Clin Pathol 30, 267–276 (2021). https://doi.org/10.1007/s00580-021-03199-z

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