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Aims: The current study was developed to investigate the influence of ginger (G), ginger nanoparticles (GNPs) and ginger nano-base (GNB) on hepato-renal toxicity induced by carbon tetrachloride (CCl4) in rats in comparison with silymarin (SM).
Place and Duration of Study: Department of Biochemistry and Nutrition, Faculty of Women for Arts, Science and Education, Ain Shams University.
Methodology: Fifty-four adult male Sprague-Dawley rats were divided into 6 groups. Group (1): Rats received distilled water orally and injected intraperitoneally (i.p.) with single dose of corn oil (1 ml/kg b.wt). Group (2): Rats were injected with single dose of CCl4 diluted with corn oil (1:1) (1 ml/kg b.wt. i.p.) at the 4th week of experiment. Groups (3), (4) and (5): Rats were orally received 50 mg /kg b.wt./day of G, GNPs and GNB, respectively for 8 weeks and injected with CCl4 as group 2. Group (6): Rats were orally received 100 mg /kg b.wt /day of SM for 8 weeks and injected with CCl4 as group 2.
Results: Our results documented that injection with CCl4 caused significant increase (p<0.05) in liver function tests [serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities], kidney function tests [serum creatinine, urea, uric acid and cystatin C] and serum levels of malondialdehyde (MDA), Nitric oxide (NO), tumor necrosis factor- alpha (TNF- α) and interleukin 1 beta (IL-1β). On the other hand, there was a significant decrease (p<0.05) in the serum total antioxidant capacity (TAC), Hepatic catalase (CAT) and superoxide dismutase (SOD) enzymes activity, with histopathological changes in liver and kidneys tissues. Oral administration of G, GNPs, GNB and SM caused an enhancement of liver and kidney function, decreasing serum oxidants and inflammatory markers levels while increasing the activities of antioxidant enzymes, also an improvement of organs histopathological changes was observed.
Conclusion: Our data proved that using ginger in the form of GNPs and GNB are more efficient in ameliorating hepato-renal toxicity induced by CCl4 than using native ginger as evidenced by biochemical analysis and histological examination of liver and kidneys tissues.
Elzwi S. Effect of Zingiber officinale (Ginger) extract on acetaminophen- induced hepatotoxicity in mice. Pharmaceutical Methods. 2019;10(1):27- 30.
Popović D, Kocić G, Katić V, Jović Z, Zarubica A, Veličković, LJ, Nikolić V, Jović A, Kundalić B, Rakić V, Ulrih NP, Skrt M, Sokolović D, Dinić L, Stojanović, M, Milosavljević A, Filip V, Sokolović D. Protective effects of anthocyanins from bilberry extract in rats exposed to nephrotoxic effects of carbon tetrachloride, Chemico-Biological Interactions. 2019; 304:61–72.
Fahmy MA, Diab KA, Abdel-Samie NS, Omara EA, Hassan ZM. Carbon tetrachloride induced hepato/renal toxicity in experimental mice: antioxidant potential of Egyptian Salvia officinalis L essential oil. Environmental Science and Pollution Research. 2018;25:27858–27876.
Ghadi FE, Ghara AR, Rodbari Z. Ameliorating effect of gamma irradiated chicory against carbon tetra-chloride induced kidney and testis damage in rat. Iranian Journal of Health Sciences. 2019; 7(1): 9-17.
Ayanniyi RO, Olumoh-Abdul HA, Ojuade FI, Abdullahi R, Anafi SB. The protective effect of Croton zambesicus against carbon tetrachloride-induced renal toxicity in rats. Iranian Journal of Toxicology. 2019; 13 (1):5 – 8.
Akbari A, Nasiri K, Heydari M, Nimrouzi M, Afsar T. Ameliorating potential of ginger (Zingiber officinale Roscoe) extract on liver function and oxidative stress induced by ethanol in male rats. Zahedan Journal of Research in Medical Science. 2019;21(2): 1- 8.
Hemieda FAE, El-Kholy WM, Masud ASA. Evaluating the protective impact of ginger extract against ciprofloxacin-induced hepatotoxicity in male albino rats. IOSR Journal of Pharmacy and Biological Sciences. 2019;14(1):23-30.
Shirpoor A, Rezaei F, Fard AA, Afshari AT, Gharalari FH, Rasmi Y. Ginger extract protects rat’s kidneys against oxidative damage after chronic ethanol adminis-tration. Biomedicine & Pharmacotherapy. 2016;84:698–704.
Al Shammari AMN. Protective effect of ginger (Zingiber officinale) consumption against kidney damage in rats. Life Science Journal. 2018;15(1):80–85.
Korni FMM, Khalil F. Effect of ginger and its nanoparticles on growth performance, cognition capability, immunity and prevention of motile Aeromonas septicaemia in Cyprinus carpio fingerlings. Aquaculture Nutrition. 2016;23:1492–1499.
Zhang M, Viennois E, Prasad M, Zhang Y, Wang L, Zhang Z, Han MK, Xiao B, Xu C, Srinivasan S, Merlin D. Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials. 2016;1- 62.
Mehanna MS, Al-Shahed FNM, Taha MK. Histological study of effect of exposure to emamectin benzoate on the kidney of adult male albino rats and the possible protective effect of ginger nanoparticles. The Egyptian Journal of Hospital Medicine. 2019;76(1):3299-3306.
Abdu SB, Abdu F, Khalil WKB. Ginger nanoparticles modulate the apoptotic activity in male rats exposed to dioxin-induced cancer initiation. International Journal of Pharmacology. 2017;13:946-957.
Bakr AF, Abdelgayed SS, EL-Tawil OS, Bakeer AM. Assessment of ginger extract and ginger nanoparticles protective activity against acetaminophen-induced hepato-toxicity and nephrotoxicity in rats. Pakistan Veterinary Journal. 2019;1-8.
Zhang H, Wang Q, Sun C, Zhu Y, Yang Q, Wei Q, Chen J, Deng W, Frimpong MA, Yu J, Xu X. Enhanced oral bioavailability, anti-tumor activity and hepatoprotective effect of 6-shogaol loaded in a type of novel micelles of polyethylene glycol and linoleic acid conjugate. Pharmaceutics. 2019; 11(107):1- 16.
Hassan SK, Mousa AM, Eshak MG, Farrag AH, Badawi AM. Therapeutic and chemo preventive effects of nano curumin against diethylnitrosamino induced hepatocellular carcinoma in rats. International Journal of Pharmacy and Pharmaceutical Sciences. 2014; 6:54- 62.
Sharifi-Rigi1 A, Heidarian E. Protective and anti-inflammatory effects of silymarin on paraquat-induced nephrotoxicity in rats. Journal of Herbmed Pharmacology. 2019; 8:28 - 34.
Mashayekhi M. Renoprotective effect of silymarin on gentamicin-induced nephropathy. African Journal of Pharmacy and Pharmacology. 2012;6(29): 2241-2246.
Amin KA, Ahmed RR, Hozayen WG, Antar A. Renoprotective and antioxidant effects of silymarin and propolis on diclofenac sodium - induced renal toxicity in rats. International Journal for Pure and Applied Bioscience. 2017;5(2):31-42.
Cengiz M. Renoprotective effects of Silybum marianum (L.) Gaertn (Silymarin) on thioacetamide-induced renal injury: Biochemical and histopathological approach. Pak. J. Pharm. Sci. 2018;31(5): 2137-2141.
Korni FMM, Khalil F. Effect of ginger and its nanoparticles on growth performance, cognition capability, immunity and prevention of motile Aeromonas septicaemia in Cyprinus carpio fingerlings. 2016;23:1492–1499.
Thakur PY, Ram MY, Dinesh PS. Mechanical milling: A top down approach for the synthesis of nanomaterials and nanocomposites. Nanoscience and Nanotechnology. 2012;2:22–48.
Eren D, Betul YM. Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3β and β-catenin pathway in A549 cell line. Chemico-Biological Interactions. 2016;1-26.
Singleton VL, Orthofer F, Lamuela-Raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin - ciocalteu reagent. Methods in Enzymology. 1999;299:152-178.
Arvouet-Grand A, Vennat B, Pourrat A, Legret P. Standardisation d'un extrait de propolis et identification des principaux constituants. Journal de Pharmacie de Belgique. 1994;49:462-468.
Cafino EJ, Marcelina BL, Eufrocinio CM. NA simple HPLC Method for the Analysis of -Gingerol Produced by Multiple Shoot Culture of Ginger (Zingiber officinale). International Journal of Pharmacognosy and Phytochemical Research. 2016;8(1): 38-42.
Sreelatha S, Padma PR, Umadevi M. Protective effects of Coriandrum sativum extracts on carbon tetrachloride-induced hepatotoxicity in rats. Food and Chemical Toxicology. 2009;47:702–708.
Murray RL. alanine aminotransferase, Kaplan A et al Clin Chem The C.V. Mosby Co, St Louis, Toronto, Princeton. 1984; 1261–1266.
Belfield A, Goldberg DM. Revised assay for serum phenyl phosphatase activity using 4- amino – antipyrine. Enzyme. 1971;12(5):561-573.
Murray RL. Creatinine, Kaplan A, et al. Clin Chem the C.V. Mosby Co, St Louis, Toronto, Princeton. 1984;1261–1266.
Kaplan A. Urea, Kaplan A, et al. Clin Chem The CV Mosby Co St Louis. Toronto. Princeton. 1984;1257-1260:437-418.
Fossati P, Prencipe L, Berti G. Use of 3, 5-dichloro-2-hydroxybenzenesulfonicacid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clinical Chemistry. 1980;26: 227-231.
Pergande M, Jung K. Sandwich Enzyme Immunoassay of Cystatin C in Serum with Commercially Available Antibodies. Clinical Chemistry. 1993;39(9):1885- 1890.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL. A meta-analysis of cytokines in major depression. Biological Psychiatry. 2010; 67:446–457.
Garabedian BS, Poole S, Allchorne A, Winter J, Woolf CJ. Contribution of interleukin- 1 to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. British Journal of Pharmacology. 1995;115:1265-1275.
Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V. Method for the measurement of antioxidant activity in human fluids, journal of clinical pathology. 2001;54:356–361.
Aebi H. Oxidoreductases acting on groups other than CHOH: catalase. Methods in Enzymology. 1984;121–126.
Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and biophysical research communication. 1972;(2) 46:849- 854.
Montgomery HAC, Dymock JF. The determination of nitrite in water. Analyst. 1961;86:414–416.
Satoh K. Serum lipid peroxide in cerebrovascular disorder determined by a new colorimetric method. Clinica Chimica Acta. 1978;90:37-43.
Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. Philadelphia: Churchill Livingstone, Elsevier; 2008.
Levesque S. SPSS programming and data management: A Guide for SPSS and SAS users, fourth edition. Spss Inc, Chicago; 2007.
Rahimi HR, Nedaeinia R, Shamloo AS, Nikdoust S, Oskuee RK. Novel delivery system for natural products: Nano-curcumin formulations. Avicenna Journal of Phytomedicine. 2016;6(4):383-398.
Mošovská S, Nováková D, Kaliňák M. Antioxidant activity of ginger extract and identification of its active components. Acta Chimica Slovaca. 2015;8(2):115—119.
Wijayanti II, Budiharjo A, Pangastut A, Prihapsara F, Artanti AN. Total phenolic content and antioxidant activity of ginger extract and SNEDDS with eel fish bone oil (Anguilla spp.). Nusantara Bioscience. 2018;10(3):164-169.
Mojzer EB, Hrnˇciˇc MK, Škerge M, Knez Z, Bren U. Polyphenols: Extraction methods, antioxidative action, bioavail-ability and anticarcinogenic effects. Molecules. 2016;21(901):1- 38.
Shirin APR, Prakash J. Chemical composition and antioxidant properties of ginger root (Zingiber officinale). Journal of Medicinal Plants Research. 2010;4(24): 2674-2679.
Bellassoued K, Hsouna AB, Athmouni K, Pelt JV, Ayadi MF, Rebai T, Elfeki A. Protective effects of Mentha piperita L. Leaf essential oil against CCl4induced hepatic oxidative damage and renal failure in rats. Lipids in Health and Disease. 2018; 17(9):1-14.
Hikal AH, Abd El-Fatta HM, El-Sheik NM, Refaie AA. Comparative study of marjoram (Origanum majorana L.) and silymarin (Silybum marianum L.) extract against carbon tetrachloride induced hepatic injury. World Journal of Pharmacy and Pharmaceutical Sciences. 2018;7(8):1969-92.
Ullah H, Khan A, Baig MW, Ullah N, Ahmed N, Tipu MK, Ali H, Khan S. Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice. BMC Complementary Medicine and Therapies. 2020;20(115):1-14.
Okda TM, Abd-Alhaseeb MM, Barka K, Ragab NM. Ginger potentiates the effects of silymarin on liver fibrosis induced by CCL4: The role of galectin-8, European Review for Medical and Pharmacological Sciences. 2019;23:885-891.
Ojarudi M, Moradi A, Hajihosseini R, Mazani M, Rezagholizadeh L. Hepatoprotective and antioxidant a ctivities of combination of Cinnamomum zeylanicum and Zingiber officinale in ccl4 -intoxicated rats. Journal of Kerman University of Medical Sciences. 2020; 27(1):1- 13.
Wang B, Zhuang X, Deng ZB, Jiang H, Mu J, and Wang Q, et al. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Molecular Therapy. 2014;22: 522- 34.
Zhuang X, Deng ZB, Mu J, Zhang L, Yan J, Miller D, Feng W, McClain CJ, Zhang HG. Ginger-derived nanoparticles protect against alcohol-induced liver damage. Journal of Extracellular Vesicles. 2015; 4.
Javed S, Ahsan W, Kohli K. Pharmacological influences of natural products as bioenhancers of silymarin against carbon tetrachloride-induced hepatotoxicity in rats. Clinical Phyto-science. 2018;4-18.
Zaki DA, Abdel-Ghany AS, Gomaa A. Therapeutic effect of milk thistle (Silybum marianum L) seeds on carbon tetrachloride - induced hepatotoxicity in rats. Alexandria Science Exchange Journal. 2019;40(1):20-29.
Bektur NE, Sahin E, Baycu C, Unver G. Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice. Toxicology and Industrial Health. 2013;1-12.
Abdel Maksoud HA, Abdel Magid AD, Mostafa YM, Elharrifc MG, Sorour RI, Sorour MI. Ameliorative effect of liquorice extract versus silymarin in experimentally induced chronic hepatitis: A biochemical and genetical study, Clinical Nutrition Experimental. 2019;23: 69-79.
Kheiripour N, Karimi J, Khodadadi I, Tavilani H, Goodarzi MT, Hashemnia M. Hepatoprotective effects of silymarin on liver injury via irisin upregulation and oxidative stress reduction in rats with type 2 diabetes. Iran J Med Sci. 2019;44(2): 108-117.
Akram MA, Tembhre M, Jabeen R, Khalid S, Sheikh MA, Jan A, Farooq U, Amin M. Defensive role of Rosmarinus officinalis in carbon tetrachloride-induced nephro-toxicity and oxidative stress in rats. Bulletin of the National Research Centre. 2019; 43(50):1- 10.
Tousson E, Keshta ATH, Hussein Y, Fekry RM, Abo-Ghaneima WK. Renal protective effect of Ginkgo biloba and l-carnitine extracts against pentylenetetrazol induced toxicity, oxidative stress, injury and proliferation alternation in epileptic rats. Annual Research & Review in Biology. 2019;32(2):1-13.
Abdulhameed IS, Al-Mohamadamin DFH, Abed AB, Abid WB. The effect of ginger plant (Zingiber officinale) aqueous extract on function and histological structure of kidney in mice treated with carbon tetrachloride. International Journal of ChemTech Research. 2017;10(12):208-219.
Joshi D, Srivastav SK, Belemkar S, Dixit VA. Zingiber officinale and 6- gingerol alleviate liver and kidney dysfunctions and oxidative stress induced by mercuric chloride in male rats: A protective approach. Biomedicine & Pharmacotherapy. 2017;91:645–655.
EL. Sayed, MGA, Farag EAH, Nasr HM. Protective effects of prebiotic (resistant maltodextrin) and silymarin against toxicity of carbon tetrachloride in liver rat and kidney. International Journal of Pharmacology and Toxicology. 2020;8(1): 15-28.
Meng X, Wang Z, Liang S, Tang Z, Liu J, Xin Y, Kuang H, Wang Q. Hepatoprotective effect of a polysaccharide from Radix Cyathulae officinalis Kuan against CCl4-induced acute liver injury in rat, International Journal of Biological Macromolecules. 2019;1- 22.
Abdel Salam OME, Sleem AA, Omara EA, Hassan NS. Effect of ribavirin alone or combined with silymarin on carbon tetrachloride induced hepatic damage in rats. Drug Target Insights. 2007;2:19–27.
Mansour DF, Abdallah HM, Ibrahim BMM, Hegazy RR, Esmail RSE, Abdel-Salam LO. The carcinogenic agent diethylnitrosamine induces early oxidative stress, inflammation and proliferation in rat liver stomach and colon: Protective Effect of Ginger Extract. Asian Pacific Journal of Cancer Prevention. 2019;20:2551- 2561.
Soliman MM, Elfeky AMS. Studies on the biochemical and molecular effects of some natural herbs on experimental-induced breast cancer in wistar rats. Nat J Physio, Pharm Pharmacol. 2016;6:5349-58.
Sha J, Song J, Yu M, Zhao X, Wang H, Zhang Y, Suo H. Polyphenolic extracts from Wushan tea leaves attenuate hepatic injury in CCl4-treated mice. Journal of Functional Foods. 2020;66:1-8.
Hasan IH, El-desouky MA, Abd-elaziz GM, Hozayen WG. Protective effects of Zingiber officinale against carbon tetrachloride induced liver fibrosis. International Journal of Pharmacy and Pharmaceutical Sciences. 2016;8:77-381.
Attia AMM, Ibrahim FAA, Nabil GM, Aziz SW. Antioxidant effects of ginger (Zingiber officinale Roscoe) against lead acetate-induced hepatotoxicity in rats. African Journal of Pharmacy and Pharmacology. 2013;7(20):1213-1219.
Shokrzadeh M, jouybari HB, Hosseinpour M, ziar A, Habibi E. Antioxidant and protective effect of hydroalcoholic extract of Celtis australis L. on CCl4 induced hepatotoxicity. Pharmaceutical and Biomedical Research. 2019;4(3):26– 31.
Lin TA, Ke BJ, Cheng CS, Wang JJ, Wei BL, Lee CL. Red quinoa bran extracts protects against carbon tetrachloride-induced liver injury and fibrosis in mice via activation of antioxidative enzyme systems and blocking TGF-β1 Pathway. Nutrients. 2019;11(395):1 -14.
Eltahir HM, Fawzy MA, Mohamed EM, Alrehany MA, Shehata AM, Abouzied MM. Antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrategum resin in CCl4-induced hepatotoxicity. Experimental and Therapeutic Medicine. 2020;19:1313-1321.