Carcinogenicity and proteomic analysis of N-Nitrosodiethylamine in rats
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Published:
Aug 22, 2018
Keywords:
Antioxidant Boilers Curcumin High stocking density
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Abstract
N-Nitrosodiethylamine (NDEA), a probable human carcinogen, is commonly used in rodent experimental hepatocarcinogenesis research. We evaluated both clastogenicity and carcinogenicity in rats using various concentrations of NDEA via a liver micronucleus assay and a medium-term carcinogenicity test. The administration of repeated NDEA injections ranging from 10 to 50 mg/kg bw together with partial hepatectomy resulted in significantly more liver micronuclei compared to control rats, while the mitotic index was indifferent. However, the highest dose (50 mg/kg bw) was lethal to the rats. Similarly, medium-term exposure at 100 mg/kg bw of NDEA increased the formation of glutathione S-transferase placental form (GST-P) positive foci, a preneoplastic lesion of liver cancer in rats. A proteomic analysis revealed overexpression of hepatic proteins involved in the PI3K/Akt/mTOR pathway after treatment with NDEA. This pathway may play a key role in the mechanisms that influence NDEA-initiated hepatocarcinogenesis in this model. In conclusion, the amount of NDEA used in the present study can be considered as clastogenic and carcinogenic to rat hepatocytes. This finding can further our knowledge concerning the establishment of experimental cancer chemoprevention models in rats.
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Insuan, O., Charoensin, S., Roytrakul, S., Thumvijit, T., Bunpo, P., & Wongpoomchai, R. (2018). Carcinogenicity and proteomic analysis of N-Nitrosodiethylamine in rats. Veterinary Integrative Sciences, 16(2), 109–122. Retrieved from https://he02.tci-thaijo.org/index.php/vis/article/view/124770
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References
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Liju, V.B., Jeena, K., Kuttan, R., 2013. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L). Food Chem. Toxicol. 53, 52-61.
Lin, H., Decuypere, E., Buyse, J., 2004. Oxidative stress induced by corticosterone administration in broiler chickens (Gallus gallus domesticus) 1. Chronic exposure. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 139, 737-744.
Marino, L., 2017. Thinking chickens: a review of cognition, emotion, and behavior in the domestic chicken. Anim. Cogn. 20, 127-147.
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Pamplona, R., Costantini, D., 2011. Molecular and structural antioxidant defenses against oxidative stress in animals. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R843-R863.
Panchal, H.D., Vranizan, K., Lee, C.Y., Ho, J., Ngai, J., Timiras, P.S., 2008. Early anti-oxidative and anti-proliferative curcumin effects on neuroglioma cells suggest therapeutic targets. Neurochem. Res. 33, 1701-1710.
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Rangsaz, N., Ahangaran, M.G., 2011. Evaluation of turmeric extract on performance indices impressed by induced aflatoxicosis in broiler chickens. Toxicol. Ind. Health. 27, 956-960.
Sayrafi, R., Mirzakhani, N., Mobaseri, R., 2017. Effects of turmeric (Curcuma longa) and vitamin E on histopathological lesions induced in bursa of Fabricius of broiler chicks by salinomycin. Vet. Res. Forum. 8, 231-236.
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Tankson, J.D., Vizzier-Thaxton, Y., Thaxton, J.P., May, J.D., Cameron, J.A., 2001. Stress and nutritional quality of broilers. Poult. Sci. 80, 1384-1389.
Thaxton, J.P., Puvadolpirod, S., 2000. Model of physiological stress in chickens 5. Quantitative evaluation. Poult. Sci. 79, 391-395.
Thomas, D.G., Ravindran, V., Thomas, D.V., Camden, B.J., Cottam, Y.H., Morel, P.C., Cook, C.J., 2004. Influence of stocking density on the performance, carcass characteristics and selected welfare indicators of broiler chickens. N. Z. Vet. J. 52, 76-81.
Trujillo, J., Chirino, Y.I., Molina-Jijón, E., Andérica-Romero, A.C., Tapia, E., Pedraza-Chaverrí, J., 2013. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox. Biol. 17, 448-456.
Yarru, L.P., Settivari, R.S., Gowda, N.K., Antoniou, E., Ledoux, D.R., Rottinghaus, G.E., 2009. Effects of turmeric (Curcuma longa) on the expression of hepatic genes associated with biotransformation, antioxidant, and immune systems in broiler chicks fed aflatoxin. Poult. Sci. 88, 2620-2627.
Zhang, J., Hou, X., Ahmad, H., Zhang, H., Zhang, L., Wang, T., 2014. Assessment of free radicals scavenging activity of seven natural pigments and protective effects in AAPH-challenged chicken erythrocytes. Food Chem.n145, 57-65.
Zhang, J., Hu, Z., Lu, C., Bai, K., Zhang, L., Wang, T., 2015. Effect of various levels of dietary curcumin on meat quality and antioxidant profile of breast muscle in broilers. J. Agric. Food Chem. 63, 3880-3886.
Akbarian, A., Michiels, J., Degroote, J., Majdeddin, M., Golian, A., De Smet, S., 2016. Association between heat stress and oxidative stress in poultry; mitochondrial dysfunction and dietary interventions with phytochemicals. J. Anim. Sci. Biotechnol. 7, 37.
Arshami, J., Pilevar, M., Aami Azghadi, M., Raji, A.R., 2013. Hypolipidemic and antioxidative effects of curcumin on blood parameters, humoral immunity, and jejunum histology in Hy-line hens. Avicenna J. Phytomed. 3, 178-185.
Attia, Y.A., Al-Harthi, M.A., El-Shafey, A.S., Rehab, Y.A., Kim, W.K., 2017. Enhancing tolerance of broiler chickens to heat stress by supplementation with vitamin E, vitamin c and/or probiotics. Ann. Anim. Sci. 17, 1155–1169.
Birben, E., Sahiner, U.M., Sackesen, C., Erzurum, S., Kalayci, O., 2012. Oxidative stress and antioxidant defense. World Allergy Organ. J. 5, 9–19.
Chainani-Wu, N., 2003. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J. Altern. Complement Med. 9, 161-168.
Cheng, A.L., Hsu, C.H., Lin, J.K., Hsu, M.M., Ho, Y.F., Shen, T.S., Ko, J.Y., Lin, J.T., Lin, B.R., Ming-Shiang. W., Yu, H.S., Jee, S.H., Chen, G.S., Chen, T.M., Chen, C.A., Lai, M.K., Pu, Y.S., Pan, M.H., Wang, Y.J., Tsai, C.C., Hsieh, C.Y., 2001. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 21, 2895-2900.
Dhabhar, F.S., 2002. Stress-induced augmentation of immune function–the role of stress hormones, leukocyte trafficking, and cytokines. Brain. Behav. Immun. 16, 785–798.
Dhabhar, F.S., Malarkey, W.B., Neri, E., McEwen, B.S., 2012. Stress-induced redistribution of immune cells–from barracks to boulevards to battlefields: a tale of three hormones–Curt Richter Award winner. Psychoneuroendocrinology. 37, 1345–1368.
Ericsson, M., Henriksen, R., Bélteky, J., Sundman, A., Shionoya, K., Jensen P., 2016. Long-term and transgenerational effects of stress experienced during different life phases in chickens (Gallus gallus). PLoS One. 11, e0153879.
Feddes, J.J., Emmanuel, E.J., Zuidhoft, M.J., 2002. Broiler performance, body weight variance, feed and water intake, and carcass quality at different stocking densities. Poult. Sci. 81, 774-779.
Gopi, S., Jacob, J., Mathur, K.Y., 2016. Acute and subchronic oral toxicity studies of hydrogenated curcuminoid formulation ‘CuroWhite’ in rats. Toxicol. Rep. 3, 817-825.
Guil-Guerrero, J.L., Ramos, L., Zúñiga Paredes J.C., Carlosama-Yépez, M., Moreno, C., Ruales P., 2017. Effects of turmeric rhizome powder and curcumin in poultry production. A review. J. Anim. Feed. Sci. 26, 293–302.
Gupta, K., Behera, K., Pradhan, C.R., Acharya, A.P., Sethy, K., Behera, D., Lone, S.A., Shinde, K.P., 2017. Influence of stocking density on the performance, carcass characteristics, hemato-biochemical indices of Vanaraja chickens Shailesh. Indian J. Anim. Res. 51, 939-943.
Hewlings, S.J., Kalman, D.S., 2017. Curcumin: A review of its' effects on human health. Foods. DOI: 10.3390/foods6100092.
Houshmand, M., Azhar, K., Zulkifli, I., Bejo, M.H., Kamyab, A., 2012. Effects of prebiotic, protein level, and stocking density on performance, immunity, and stress indicators of broilers. Poult. Sci. 91, 393-401.
Jayaprakasha, G.K., Jagan Mohan Rao, L., Sakariah, K.K., 2002. Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. J. Agric Food Chem. 50, 3668-3672.
Jeong, G.S., Oh, G.S., Pae, H.O., Jeong, S.O., Kim, Y.C., Shin, M.K,, Seo, B.Y., Han, S.Y., Lee, H.S., Jeong, J.G., Koh, J.S., Chung, H.T., 2006. Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection. Exp. Mol. Med. 38, 393-400.
Jiang, W., Li, Y., Sun, J., Li, L., Li, J.W., Zhang, C., Huang, C., Yang, J., Kong, G.Y., Li, Z.F., 2017. Spleen contributes to restraint stress induced changes in blood leukocytes distribution. Sci. Rep. 7, 6501. DOI: 10.1038/s41598-017-06956-9.
Kang, H.K., Park, S.B., Kim, S.H., Kim, C.H., 2016. Effects of stock density on the laying performance, blood parameter, corticosterone, litter quality, gas emission and bone mineral density of laying hens in floor pens. Poult. Sci. 95, 2764-2770.
Kuttappan, V.A., Huff, G.R., Huff, W.E., Hargis, B.M., Apple, J.K., Coon, C., Owens, C.M., 2013. Comparison of hematologic and serologic profiles of broiler birds with normal and severe degrees of white striping in breast fillets. Poult. Sci. 92, 339-345.
Lee, M.T., Lin, W.C., Yu, B., Lee, T.T., 2017. Antioxidant capacity of phytochemicals and their potential effects on oxidative status in animals - A review. Asian-Australas J. Anim. Sci. 30, 299-308.
Liju, V.B., Jeena, K., Kuttan, R., 2013. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L). Food Chem. Toxicol. 53, 52-61.
Lin, H., Decuypere, E., Buyse, J., 2004. Oxidative stress induced by corticosterone administration in broiler chickens (Gallus gallus domesticus) 1. Chronic exposure. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 139, 737-744.
Marino, L., 2017. Thinking chickens: a review of cognition, emotion, and behavior in the domestic chicken. Anim. Cogn. 20, 127-147.
Orawan, C., Aengwanich, W., 2007. Blood cell characteristics, hematological values and average daily gained weight of Thai indigenous, Thai indigenous crossbred and broiler chickens. Pak. J. Biol. Sci. 10, 302-309.
Pamplona, R., Costantini, D., 2011. Molecular and structural antioxidant defenses against oxidative stress in animals. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R843-R863.
Panchal, H.D., Vranizan, K., Lee, C.Y., Ho, J., Ngai, J., Timiras, P.S., 2008. Early anti-oxidative and anti-proliferative curcumin effects on neuroglioma cells suggest therapeutic targets. Neurochem. Res. 33, 1701-1710.
Papadopoulou, A., Petrotos, K., Stagos, D., Gerasopoulos, K., Maimaris, A., Makris, H., Kafantaris, I., Makri, S., Kerasioti, E., Halabalaki, M., Brieudes, V., Ntasi, G., Kokkas, S., Tzimas, P., Goulas, P., Zakharenko, A.M., Golokhvast, K.S., Tsatsakis, A., Kouretas, D., 2017. Enhancement of antioxidant mechanisms and reduction of oxidative stress in chickens after the administration of drinking water enriched with polyphenolic powder from olive mill waste waters. Oxid. Med. Cell. Longev. DOI: 10.1155/2017/8273160.
Pimson, C., Chatuphonprasert, W., Jarukamjorn, K., 2014. Improvement of antioxidant balance in diabetes mellitus type 1 mice by glutathione supplement. Pak. J. Pharm. Sci. 27, 1731-1737.
Post, J., Rebel, J.M., ter Huurne, A.A., 2003. Physiological effects of elevated plasma corticosterone concentrations in broiler chickens. An alternative means by which to assess the physiological effects of stress. Poult. Sci. 82, 1313-1318.
Rangsaz, N., Ahangaran, M.G., 2011. Evaluation of turmeric extract on performance indices impressed by induced aflatoxicosis in broiler chickens. Toxicol. Ind. Health. 27, 956-960.
Sayrafi, R., Mirzakhani, N., Mobaseri, R., 2017. Effects of turmeric (Curcuma longa) and vitamin E on histopathological lesions induced in bursa of Fabricius of broiler chicks by salinomycin. Vet. Res. Forum. 8, 231-236.
Simitzis, P.E., Kalogeraki, E., Goliomytis, M., Charismiadou, M.A., Triantaphyllopoulos, K., Ayoutanti, A., Niforou, K., Hager-Theodorides, A.L., Deligeorgis, S.G., 2012. Impact of stocking density on broiler growth performance, meat characteristics, behavioural components and indicators of physiological and oxidative stress. Br. Poult. Sci. 53, 721-730.
Stukelj, M., Toplak, I., Svete, A.N., 2013. Blood antioxidant enzymes (SOD, GPX), biochemical and haematological parameters in pigs naturally infected with porcine reproductive and respiratory syndrome virus. Pol. J. Vet. Sci. 16, 369-376.
Tankson, J.D., Vizzier-Thaxton, Y., Thaxton, J.P., May, J.D., Cameron, J.A., 2001. Stress and nutritional quality of broilers. Poult. Sci. 80, 1384-1389.
Thaxton, J.P., Puvadolpirod, S., 2000. Model of physiological stress in chickens 5. Quantitative evaluation. Poult. Sci. 79, 391-395.
Thomas, D.G., Ravindran, V., Thomas, D.V., Camden, B.J., Cottam, Y.H., Morel, P.C., Cook, C.J., 2004. Influence of stocking density on the performance, carcass characteristics and selected welfare indicators of broiler chickens. N. Z. Vet. J. 52, 76-81.
Trujillo, J., Chirino, Y.I., Molina-Jijón, E., Andérica-Romero, A.C., Tapia, E., Pedraza-Chaverrí, J., 2013. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox. Biol. 17, 448-456.
Yarru, L.P., Settivari, R.S., Gowda, N.K., Antoniou, E., Ledoux, D.R., Rottinghaus, G.E., 2009. Effects of turmeric (Curcuma longa) on the expression of hepatic genes associated with biotransformation, antioxidant, and immune systems in broiler chicks fed aflatoxin. Poult. Sci. 88, 2620-2627.
Zhang, J., Hou, X., Ahmad, H., Zhang, H., Zhang, L., Wang, T., 2014. Assessment of free radicals scavenging activity of seven natural pigments and protective effects in AAPH-challenged chicken erythrocytes. Food Chem.n145, 57-65.
Zhang, J., Hu, Z., Lu, C., Bai, K., Zhang, L., Wang, T., 2015. Effect of various levels of dietary curcumin on meat quality and antioxidant profile of breast muscle in broilers. J. Agric. Food Chem. 63, 3880-3886.