Abstract
This study aimed to examine the protective effects of ginger (G) on the genetic response induced by cadmium (Cd) and immunohistochemical expression of Caspase3 and MKI67 in the kidney and liver of rabbits. Male rabbits were divided into three groups; each group contains 10 animals: group (C) received basic diet and tap water for 12 weeks, the second group (Cd) received 200 mg/kg b.w CdCl2 in water for 12 weeks, group (Cd + G) was given 200 mg/kg b.w CdCl2 in water and 400 mg ginger/kg b.w in food for 12 weeks. Cd administration increased the activity of mRNA expression of the examined apoptotic (Caspase3), proliferation (MKI67), proto-oncogene (C-fos), and antioxidant (GST), while decreased the expression of anti-apoptotic (Bcl2). Ginger counteracted the effects of Cd in (Cd + G) group and downregulated the previously upregulated genes under Cd administration appeared in (Cd) group. The immunohistochemical expression of Caspase3 and MKI67 in the liver and kidney cells of the (C) group was shown very faint to negative reactions, strong staining in hepatocytes and the tubular epithelium in cadmium-treated group, while slight staining in some hepatocytes and tubular epithelium in co-administration with ginger in (Cd + G) group. In conclusion, ginger administration showed a protective effect against cadmium toxicity.
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Chargui A, Zerki S, Jacquillet G, Rubera I et al (2011) Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicol Sci 121(1):31–42. doi:10.1093/toxsci/kfr031
Jie L, Junfeng L, Xingzhong Y, Haoran D, Guangming Z et al (2015) Facile synthesis of alumina-decorated multi-walled carbon nanotubes for simultaneous adsorption of cadmium ion and trichloroethylene. Chem Eng J 273:101–110
Lin YS, Caffrey JL, Chang MH, Dowling N, Lin JW (2010) Cigarette smoking, cadmium exposure, and zinc intake on obstructive lung disorder. Respir Res 11:53. doi:10.1186/1465-9921-11-53
Duruibe JO, Ogwuegbu MOC, Egwurugwu JN (2007) Heavy metal pollution and human biotoxic effects. Int J Phys Sci 2(5):112–118
Selena M, Alessandro C, Massimo P, Giacomo C (2012) Remediation of heavy metals contaminated. Soils by ball milling. Chem Eng Trans 28:187–192
Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez-Ruiz MC (2012) Liver and cadmium toxicity. J Drug Metab Toxicol S5:001. doi:10.4172/2157-7609.S5-001
Cobbina SJ, Chen Y, Zhou Z, Wu X, Feng W, Wang W, Mao G, Xu H, Zhang Z, Wu X, Yang L (2015) Low concentration toxic metal mixture interactions: effects on essential and non-essential metals in brain, liver, and kidneys of mice on sub-chronic exposure. Chemosphere 132:79–86. doi:10.1016/j.chemosphere.2015.03.013, Epub 2015 Mar 28
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382(9888):260–72. doi:10.1016/S0140-6736(13)60687-X, Epub 2013 May 31
Cedergreen N (2014) Quantifying synergy: a systematic review of mixture toxicity studies within environmental toxicology. PLoS ONE 9:e96580. doi:10.1371/journal.pone.0096580
Yang H, Shu Y (2015) Cadmium transporters in the kidney and cadmium-induced nephrotoxicity. Int J Mol Sci 16(1):1484–94. doi:10.3390/ijms16011484
Johri N, Jacquillet G, Unwin R (2010) Heavy metal poisoning: the effects of cadmium on the kidney. Biometals 23(5):783–92. doi:10.1007/s10534-010-9328-y, Epub 2010 Mar 31
Chargui A, Zekri S, Jacquillet G, Rubera I, Ilie M, Belaid A, Duranton C, Tauc M, Hofman P, Poujeol P, El May MV, Mograbi B (2011) Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicol Sci 121(1):31–42. doi:10.1093/toxsci/kfr031, Epub 2011 Feb 15
IARC (1993) Cadmium and cadmium compounds. IARC Monogr Eval Carcinog Risks Hum 58:119–237
Whitfield JB, Dy V, McQuilty R, Zhu G, Heath AC, Montgomery GW, Martin NG (2010) Genetic effects on toxic and essential elements in humans: arsenic, cadmium, copper, lead, mercury, selenium, and zinc in erythrocytes. Environ Health Perspect 118(6):776–82. doi:10.1289/ehp.0901541, Epub 2010 Jan 5
Joseph P (2009) Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol 238(3):272–9. doi:10.1016/j.taap.2009.01.011, Epub 2009 Feb 6
Méndez-Couz M, Conejo NM, Vallejo G, Arias JL (2014) Spatial memory extinction: a c-Fos protein mapping study. Behav Brain Res 260:101–10. doi:10.1016/j.bbr.2013.11.032, Epub 2013 Dec 4
Vanelzakker MB, Zoladz PR, Thompson VM, Park CR, Halonen JD, Spencer RL, Diamond DM (2011) Influence of pre-training predator stress on the expression of c-fos mRNA in the hippocampus, amygdala, and striatum following long-term spatial memory retrieval. Front Behav Neurosci 5:30. doi:10.3389/fnbeh.2011.00030, eCollection 2011
Lin X, Fang Q, Chen S, Zhe N, Chai Q, Yu M, Zhang Y, Wang Z, Wang J (2015) Heme oxygenase-1 suppresses the apoptosis of acute myeloidleukemia cells via the JNK/c-JUN signaling pathway. Leuk Res 39(5):544–52. doi:10.1016/j.leukres.2015.02.009, Epub 2015 Mar 20
Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283(2–3):65–87. doi:10.1016/j.tox.2011.03.001, Epub 2011 Mar 23
Gürpinar T, Ekerbicer N, Uysal N, Barut T, Tarakci F, Tuglu MI (2012) The effectsof the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain. Sci World J 2012:498489. doi:10.1100/2012/498489
Övey IS, Naziroğlu M (2015) Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience 284:225–33. doi:10.1016/j.neuroscience.2014.09.078, Epub 2014 Oct 8
Arini A, Gourves PY, Gonzalez P, Baudrimont M (2015) Metal detoxification and gene expression regulation after a Cd and Zn contamination: an experimental study on Danio rerio. Chemosphere 128:125–33. doi:10.1016/j.chemosphere.2015.01.022, Epub 2015 Feb 16
Yadav P, Chatterjee A, Bhattacharjee A (2014) Identification of deleterious nsSNPs inα, μ, π and θ class of GST family and their influence on protein structure. Genomics Data 2:66–72
Esteban MA, Cordero H, Martínez-Tom M et al (2014) Effect of dietary supplementation of probiotics and palm fruits extracts on the antioxidant enzyme gene expression in the mucosae of gilthead seabream (Sparus aurata L). Fish Shellfish Immunol 39(2):532–40. doi:10.1016/j.fsi.2014.06.012
Bautista-Covarrubias JC, Velarde-Montes GJ, Voltolina D et al (2014) Humoral and haemocytic responses of Litopenaeus vannamei to Cd exposure. Sci World J 2014:903452. doi:10.1155/2014/903452
Peng T, Wang WN, Gu MM, Xie CY, Xiao YC, Liu Y, Wang L (2015) Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in litopenaeus vannamei. Aquat Toxicol 163:89–96. doi:10.1016/j.aquatox.2015.03.023, Epub 2015 Apr 1
Belzacq A, Vieira HLA, Verrier F, Cohen I, Larquet E et al (2003) Bcl-2 and Bax modulate adenine nucleotide translocase activity. Cancer Res 63(2):541–6
Petanidis S, Hadzopoulou-Cladaras M, Salifoglou A (2013) Cadmium modulates H-ras expression and caspase-3 apoptotic cell death in breast cancer epithelial MCF-7 cells. J Inorg Biochem 121:100–7. doi:10.1016/j.jinorgbio.2012.12.015, Epub 2013 Jan 7
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281(5381):1312–6
Woo M, Hakem R, Soengas MS, Duncan GS, Shahinian A, Kägi D et al (1998) Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev 12(6):806–19
Zhang X, Barile G, Chang S, Hays A, Pachydaki S, Schiff W, Sparrow J (2005) Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression. Curr Eye Res 30(5):395–403
Templeton N, Lewis A, Dorai H, Qian EA, Campbell MP, Smith KD et al (2014) The impact of anti-apoptotic gene Bcl-2Δ expression on CHO central metabolism. Metab Eng 25:92–102. doi:10.1016/j.ymben.2014.06.010, Epub 2014 Jul 8
Bonhin RG, Carvalho GM, Guimarães AC, Chone CT, Crespo AN, Altemani AM, Amstalden EM (2014) Histologic correlation of expression of Ki-67 in squamous cell carcinoma of the glottis according to the degree of cell differentiation. Braz J Otorhinolaryngol 80(4):290–5. doi:10.1016/j.bjorl.2014.05.016, Epub 2014 Jun 11
Sasaki K, Murakami T, Kawasaki M, Takahashi M (1987) The cell cycle associated change of the Ki-67 reactive nuclear antigen expression. J Cell Physiol 133(3):579–84
Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182(3):311–22
Noori S (2012) An overview of oxidative stress and antioxidant defensive system. 1:413. doi:10.4172/scientificreports.413
Mansour AA, Salam MA, Saad YM (2012) Mice (Mus musculus) genome responses to methotrexate (MTX) and some plant extracts. Life Sci J 9(4):4881–4886
Hosseinimehr SJ (2014) Beneficial effects of natural products on cells during ionizing radiation. Rev Environ Health. doi:10.1515/reveh-2014-0037
Ramudu SK, Korivi M, Kesireddy N, Chen CY, Kuo CH, Kesireddy SR (2011) Ginger feeding protects against renal oxidative damage caused by alcohol consumption in rats. J Ren Nutr 21(3):263–70. doi:10.1053/j.jrn.2010.03.003, Epub 2010 Jul 5
Gümüşay ÖA, Borazan AA, Ercal N, Demirkol O (2015) Drying effects on the antioxidant properties of tomatoes and ginger. Food Chem 173:156–62. doi:10.1016/j.foodchem.2014.09.162, Epub 2014 Oct 7
Egwurugwu JN, Ufearo CS, Abanobi OC et al (2007) Effects of ginger (Zingiber officinale) on cadmium toxicity. Afr J Biotechnol 6:2078–82
Onwuka FC, Erhabor O, Eteng MU, Umoh IB (2011) Protective effects of ginger toward cadmium-induced tests and kidney lipid peroxidation and hematological impairment in albino rats. J Med Food 14(7–8):817–21. doi:10.1089/jmf.2010.0106, Epub 2011 Apr 10
Al-Ameer HA (2012) Study the adverse role of histological and oxidative effects of ginger (Zingiberaceae) and cadmium chloride in liver tissue of rabbits. Kufa J Vet Med Sci 3(1):27–35
Attia HF, Kandiel MM, Ismail TA, Soliman MM, Nassan MA, Mansour AA (2012) Immunohistochemical, cellular localization and expression of inhibin hormone in the buffalo (Bubalus bubalis) adenohypophysis at different ages. J Vet Anat 5(2):83–104
Kiernan J (2008) Methods for connective tissue. In: Kiernan JA (ed) Histological and histochemical methods:theory and practice, 4th edn. Scion, Bloxham, p 190–213
Horiguchi N, Ishac EJ, Gao B (2007) Liver regeneration is suppressed in alcoholic cirrhosis: correlation with decreased STAT3 activation. Alcohol 41(4):271–80
Nair PM, Choi J (2011) Identification, characterization and expression profiles of chironomus Riparius glutathione S-transferase (GST) genes in response to cadmium and silver nanoparticles exposure. Aquat Toxicol 101(3–4):550–60. doi:10.1016/j.aquatox.2010.12.006, Epub 2010 Dec 17
Creagh EM, Conroy H, Martin SJ (2003) Caspase-activation pathways in apoptosis and immunity. Immunol Rev 193:10–21
Yagihashi S, Miura Y, Yagasaki K (2008) Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture. Cytotechnology 57(2):129–36. doi:10.1007/s10616-008-9121-8
Nigam R, Linshy VN, Kurtarkar SR, Saraswat R (2009) Effects of sudden stress due to heavy metal mercury on benthic foraminifer Rosalina leei: laboratory culture experiment. Mar Pollut Bull 59(8–12):362–8. doi:10.1016/j.marpolbul.2009.08.014
Keum YS, Kim J, Lee KH, Park KK, Surh YJ, Lee JM et al (2002) Induction of apoptosis and caspase-3 activation by chemopreventive 6-paradol and structurally related compounds in KB cells. Cancer Lett 177(1):41–7
Ghasemzadeh A, Hawa ZEJ, Rahmat A (2010) Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules 15:4324–4333. doi:10.3390/molecules15064324
Min JIB, Ok S, Mira J, Woo-Sik J (2012) 6-shogaol-rich extract from ginger up-regulates the antioxidant defense systems in cells and mice. Molecules 17:8037–8055. doi:10.3390/molecules17078037
Chen YT, Henk MJ, Carney KJ, Wong WD et al (1997) Prognostic significance of tumor markers in colorectal cancer patients: DNA index, S-phase fraction, p53 expression, and Ki-67 index. J Gastrointest Surg 1(3):266–72, discussion 273
Baiomy A, Attia H, Soliman M, Makrum O (2015) Protective effect of ginger and zinc chloride mixture on the liver and kidney alterations induced by malathion toxicity. Int J Immunopathol Pharmacol 28(1):122–8. doi:10.1177/0394632015572083
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Baiomy, A.A., Mansour, A.A. Genetic and Histopathological Responses to Cadmium Toxicity in Rabbit’s Kidney and Liver: Protection by Ginger (Zingiber officinale). Biol Trace Elem Res 170, 320–329 (2016). https://doi.org/10.1007/s12011-015-0491-4
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DOI: https://doi.org/10.1007/s12011-015-0491-4