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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Nickel and Oxidative Stress: Cell Signaling Mechanisms and Protective Role of Vitamin C

Author(s): Swastika Das, Rachamalla C. Reddy, Kailash S. Chadchan, Arun J. Patil, Mallanagouda S. Biradar and Kusal K. Das*

Volume 20, Issue 7, 2020

Page: [1024 - 1031] Pages: 8

DOI: 10.2174/1871530319666191205122249

Price: $65

Abstract

Background: Nickel activates the signaling pathways through the oxygen sensing mechanism and the signaling cascades that control hypoxia-inducible transcriptional gene expressions through oxidative stress. This review emphasizes on the recent updates of nickel toxicities on oxidant and antioxidant balance, molecular interaction of nickel and its signal transduction through low oxygen microenvironment in the in-vivo physiological system.

Discussion: Nickel alters intracellular chemical microenvironment by increasing ionized calcium concentration, lipid peroxidation, cyclooxygenase, constitutive nitric oxide synthase, leukotriene B4, prostaglandin E2, interleukins, tumor necrosis factor-α, caspases, complement activation, heat shock protein 70 kDa and hypoxia-inducible factor-1α. The oxidative stress induced by nickel is responsible for the progression of metastasis. It has been observed that nickel exposure induces the generation of reactive oxygen species which leads to the increased expression of p53, NF-kβ, AP-1, and MAPK. Ascorbic acid (vitamin C) prevents lipid peroxidation, oxidation of low-density lipoproteins and advanced oxidation protein products. The mechanism involves that vitamin C is capable of reducing ferric iron to ferrous iron in the duodenum, thus the availability of divalent ferrous ion increases which competes with nickel (a divalent cation itself) and reduces its intestinal absorption and nickel toxicities.

Conclusion: Reports suggested the capability of ascorbic acid as a regulatory factor to influence gene expression, apoptosis and other cellular functions of the living system exposed to heavy metals, including nickel.

Keywords: Antioxidant, cyclooxygenase, hypoxia-inducible factor-1α, nickel, oxidative stress, tumor necrosis factor-α.

Graphical Abstract
[1]
Das, K.K.; Das, S.N.; Dhundasi, S.A. Nickel: Molecular Diversity, Application, Essentiality and Toxicity in Human Health. In: Biometals: Molecular Structures, Binding Properties and Applications; Nova Science Publishers Inc, 2010; pp. 33-58.
[2]
Royal Society of Chemistry. Elements and Periodic Table History., http://www.rsc.org/periodic-table/element/28/nickel
[3]
Ahamed, M.; Akhtar, M.J.; Siddiqui, M.A.; Ahmad, J.; Musarrat, J.; Al-Khedhairy, A.A.; AlSalhi, M.S.; Alrokayan, S.A. Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells. Toxicology, 2011, 283(2-3), 101-108.
[http://dx.doi.org/10.1016/j.tox.2011.02.010] [PMID: 21382431]
[4]
Suparman, E.; Smf, B.; Kedokteran, F.; Sam, U.; Manado, R.; Manado, R.D.K. Peran GnRH Agonis. Biomedik, (JBM). 2016, 8(1), 1-7.
[5]
Greenwood, A. Earnshaw Butterworth –Heinemann. In: Chemistry of the Elements, 2nd ed; N.N. Oxford, 1997.
[6]
Coogan, T.P.; Latta, D.M.; Snow, E.T.; Costa, M. Toxicity and carcinogenicity of nickel compounds. Crit. Rev. Toxicol., 1989, 19(4), 341-384.
[http://dx.doi.org/10.3109/10408448909029327] [PMID: 2663022]
[7]
Croteau, M.N.; Luoma, S.N. Predicting dietborne metal toxicity from metal influxes. Environ. Sci. Technol., 2009, 43(13), 4915-4921.
[http://dx.doi.org/10.1021/es9007454] [PMID: 19673285]
[8]
Costa, M.; Mollenhauer, H.H. Carcinogenic activity of particulate nickel compounds is proportional to their cellular uptake. Science, 1980, 209(4455), 515-517.
[http://dx.doi.org/10.1126/science.7394519] [PMID: 7394519]
[9]
Das, K.K.; Das, S.N.; Dhundasi, S.A. Nickel: Molecular Diversity, Application, Essentiality and Toxicity in Human Health.; Biometals: Molecular Structures; Binding Properties and Applications, 2010, pp. 33-58.
[10]
Das, K.K.; Das, S.N.; Dhundasi, S.A. Nickel, its adverse health effects & oxidative stress. Indian J. Med. Res., 2008, 128(4), 412-425.
[PMID: 19106437]
[11]
ATSDR, U.S. Department of Health and Human Services. Toxicological Profile for Nickel, 2005.
[12]
He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell. Physiol. Biochem., 2017, 44(2), 532-553.
[http://dx.doi.org/10.1159/000485089] [PMID: 29145191]
[13]
Jargar, J.G.; Yendigeri, S.M.; Hattiwale, S.H.; Dhundasi, S.A.; Das, K.K. α-Tocopherol ameliorates nickel induced testicular oxidative and nitrosative stress in albino rats. J. Basic Clin. Physiol. Pharmacol., 2012, 23(2), 77-82.
[http://dx.doi.org/10.1515/jbcpp-2012-0013] [PMID: 23092795]
[14]
Deng, J.; Guo, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Wang, X.; Zhao, L. Oxidative stress and inflammatory responses involved in dietary nickel chloride (NiCl2)-induced pulmonary toxicity in broiler chickens. Toxicol. Res. (Camb.), 2016, 5(5), 1421-1433.
[http://dx.doi.org/10.1039/C6TX00197A] [PMID: 30090446]
[15]
Rendall, R.E.G.; Phillips, J.I.; Renton, K.A. Death following exposure to fine particulate nickel from a metal arc process. Ann. Occup. Hyg., 1994, 38(6), 921-930.
[PMID: 7825932]
[16]
Das, K.K.; Buchner, V. Effect of nickel exposure on peripheral tissues: Role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev. Environ. Health, 2007, 22(2), 157-173.
[http://dx.doi.org/10.1515/REVEH.2007.22.2.157] [PMID: 17894205]
[17]
Warner, J.S. Nickel carbonyl: Prenatal exposure. Science, 1979, 203(4386), 1194-1195.
[http://dx.doi.org/10.1126/science.424746] [PMID: 424746]
[18]
Chashschin, V.P.; Artunina, G.P.; Norseth, T. Congenital defects, abortion and other health effects in nickel refinery workers. Sci. Total Environ., 1994, 148(2-3), 287-291.
[http://dx.doi.org/10.1016/0048-9697(94)90405-7] [PMID: 8029704]
[19]
Goyer, R. Toxic effects of metals. In: Casarett and Doull’s Toxicology, 4th; Amdur, M.O.; Doull, J.D.; Klaassen, C.D., Eds.; Pergamon Press: New York, 1991; pp. 623-680.
[20]
Nicklin, S.; Nielsen, G.D. Nickel and the immune system: current concepts In: Nickel and Human Health – Current perspectives; John Wiley and Sons, Inc.: New York, . , 1992; 25, pp. 239-259.
[21]
Huang, Y.C.; Ning, H.C.; Chen, S.S.; Lin, C.N.; Wang, I.K.; Weng, S.M.; Weng, C.H.; Hsu, C.W.; Huang, W.H.; Lu, J.J.; Wu, T.L.; Yen, T.H. Survey of urinary nickel in peritoneal dialysis patients. Oncotarget, 2017, 8(36), 60469-60478.
[http://dx.doi.org/10.18632/oncotarget.19730] [PMID: 28947985]
[22]
Jouybari, L.; Saei Ghare Naz, M.; Sanagoo, A.; Kiani, F.; Sayehmiri, F.; Sayehmiri, K.; Hasanpour Dehkordi, A. Toxic elements as biomarkers for breast cancer: A meta-analysis study. Cancer Manag. Res., 2018, 10, 69-79.
[http://dx.doi.org/10.2147/CMAR.S151324] [PMID: 29391828]
[23]
Valko, M.; Morris, H.; Cronin, M.T.D. Metals, toxicity and oxidative stress. Curr. Med. Chem., 2005, 12(10), 1161-1208.
[http://dx.doi.org/10.2174/0929867053764635] [PMID: 15892631]
[24]
Das, K.K.; Reddy, R.C.; Bagoji, I.B.; Das, S.; Bagali, S.; Mullur, L.; Khodnapur, J.P.; Biradar, M.S. Primary concept of nickel toxicity - An overview. J. Basic Clin. Physiol. Pharmacol., 2018, 30(2), 141-152.
[http://dx.doi.org/10.1515/jbcpp-2017-0171] [PMID: 30179849]
[25]
Buege, J.A.; Aust, S.D. Microsomal lipid peroxidation. Methods Enzymol., 1978, 52, 302-310.
[http://dx.doi.org/10.1016/S0076-6879(78)52032-6] [PMID: 672633]
[26]
Basha, M.P.; Sujitha, N.S. Chronic fluoride toxicity and myocardial damage: antioxidant offered protection in second generation rats. Toxicol. Int., 2011, 18(2), 99-104.
[http://dx.doi.org/10.4103/0971-6580.84260] [PMID: 21976813]
[27]
Das, K.K.; Das, S.N.; DasGupta, S. The influence of ascorbic acid on nickel-induced hepatic lipid peroxidation in rats. J. Basic Clin. Physiol. Pharmacol., 2001, 12(3), 187-195.
[http://dx.doi.org/10.1515/JBCPP.2001.12.3.187] [PMID: 11762690]
[28]
Salnikow, K.; Gao, M.; Voitkun, V.; Huang, X.; Costa, M. Altered oxidative stress responses in nickel-resistant mammalian cells. Cancer Res., 1994, 54(24), 6407-6412.
[PMID: 7987835]
[29]
Chen, C.Y.; Wang, Y.F.; Lin, Y.H.; Yen, S.F. Nickel-induced oxidative stress and effect of antioxidants in human lymphocytes. Arch. Toxicol., 2003, 77(3), 123-130.
[http://dx.doi.org/10.1007/s00204-002-0427-6] [PMID: 12632251]
[30]
Topal, A.; Atamanalp, M.; Oruç, E.; Erol, H.S. Physiological and biochemical effects of nickel on rainbow trout (Oncorhynchus mykiss) tissues: Assessment of nuclear factor kappa B activation, oxidative stress and histopathological changes. Chemosphere, 2017, 166, 445-452.
[http://dx.doi.org/10.1016/j.chemosphere.2016.09.106] [PMID: 27705832]
[31]
Das, K.K.; Honnutagi, R.; Mullur, L.; Reddy, R.C.; Das, S. Majid, Dhundasi.S; Biradar, M.S. Heavy metals and low-oxygen microenvironment-its impact on liver metabolism and dietary supplementation. In: Dietary Interventions in Liver Disease; Ronald Ross Watson and Victor R. Preedy,Eds.; Elsevier Inc.. , 2019; pp. 315-332.
[32]
Locksley, R.M.; Killeen, N.; Lenardo, M.J. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell, 2001, 104(4), 487-501.
[http://dx.doi.org/10.1016/S0092-8674(01)00237-9] [PMID: 11239407]
[33]
Chuang, H.C.; Hsueh, T.W.; Chang, C.C.; Hwang, J.S.; Chuang, K.J.; Yan, Y.H.; Cheng, T.J. Nickel-regulated heart rate variability: The roles of oxidative stress and inflammation. Toxicol. Appl. Pharmacol., 2013, 266(2), 298-306.
[http://dx.doi.org/10.1016/j.taap.2012.11.006] [PMID: 23164665]
[34]
Gölz, L.; Buerfent, B.C.; Hofmann, A.; Rühl, H.; Fricker, N.; Stamminger, W.; Oldenburg, J.; Deschner, J.; Hoerauf, A.; Nöthen, M.M.; Schumacher, J.; Hübner, M.P.; Jäger, A. Genome-wide transcriptome induced by nickel in human monocytes. Acta Biomater., 2016, 43, 369-382.
[http://dx.doi.org/10.1016/j.actbio.2016.07.047] [PMID: 27477848]
[35]
Swardfager, W.; Lanctôt, K.; Rothenburg, L.; Wong, A.; Cappell, J.; Herrmann, N. A meta-analysis of cytokines in Alzheimer’s disease. Biol. Psychiatry, 2010, 68(10), 930-941.
[http://dx.doi.org/10.1016/j.biopsych.2010.06.012] [PMID: 20692646]
[36]
Dowlati, Y.; Herrmann, N.; Swardfager, W.; Liu, H.; Sham, L.; Reim, E.K.; Lanctôt, K.L. A meta-analysis of cytokines in major depression. Biol. Psychiatry, 2010, 67(5), 446-457.
[http://dx.doi.org/10.1016/j.biopsych.2009.09.033] [PMID: 20015486]
[37]
Victor, F.C.; Gottlieb, A.B. TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis. J. Drugs Dermatol., 2002, 1(3), 264-275.
[PMID: 12851985]
[38]
Ding, J.; Huang, Y.; Ning, B.; Gong, W.; Li, J.; Wang, H.; Chen, C.Y.; Huang, C. TNF-alpha induction by nickel compounds is specific through ERKs/AP-1-dependent pathway in human bronchial epithelial cells. Curr. Cancer Drug Targets, 2009, 9(1), 81-90.
[http://dx.doi.org/10.2174/156800909787313995] [PMID: 19200052]
[39]
Jaén, R.I.; Prieto, P.; Casado, M.; Martín-Sanz, P.; Boscá, L. Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer: An update. World J. Gastroenterol., 2018, 24(48), 5454-5461.
[http://dx.doi.org/10.3748/wjg.v24.i48.5454] [PMID: 30622375]
[40]
Fitzpatrick, F.A. Cyclooxygenase enzymes: regulation and function. Curr. Pharm. Des., 2004, 10(6), 577-588.
[http://dx.doi.org/10.2174/1381612043453144] [PMID: 14965321]
[41]
Ding, J.; Zhang, X.; Li, J.; Song, L.; Ouyang, W.; Zhang, D.; Xue, C.; Costa, M.; Meléndez, J.A.; Huang, C. Nickel compounds render anti-apoptotic effect to human bronchial epithelial Beas-2B cells by induction of cyclooxygenase-2 through an IKKbeta/p65-dependent and IKKalpha- and p50-independent pathway. J. Biol. Chem., 2006, 281(51), 39022-39032.
[http://dx.doi.org/10.1074/jbc.M604798200] [PMID: 16982623]
[42]
Sato, T.; Kishimoto, Y.; Asakawa, S.; Mizuno, N.; Hiratsuka, M.; Hirasawa, N. Involvement of COX-2 in nickel elution from a wire implanted subcutaneously in mice. Toxicology, 2016, 363-364, 37-45.
[http://dx.doi.org/10.1016/j.tox.2016.07.013] [PMID: 27452194]
[43]
Zhang, D.; Li, J.; Wu, K.; Ouyang, W.; Ding, J.; Liu, Z.G.; Costa, M.; Huang, C. JNK1, but not JNK2, is required for COX-2 induction by nickel compounds. Carcinogenesis, 2007, 28(4), 883-891.
[http://dx.doi.org/10.1093/carcin/bgl186] [PMID: 17065197]
[44]
Solymoss, B.; Jasmin, G. Studies of the mechanism of polycythemia induced in rats by Ni3S2. Exp. Hematol., 1978, 6(1), 43-47.
[PMID: 624333]
[45]
Morse, E.E.; Lee, T.Y.; Reiss, R.F.; Sunderman, F.W., Jr Dose-response and time-response study of erythrocytosis in rats after intrarenal injection of nickel subsulfide. Ann. Clin. Lab. Sci., 1977, 7(1), 17-24.
[PMID: 836000]
[46]
Sunderman, F.W., Jr Carcinogenicity of nickel compounds in animals. IARC Sci. Publ., 1984, (53), 127-142.
[PMID: 6532978]
[47]
Goldberg, M.A.; Dunning, S.P.; Bunn, H.F. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science, 1988, 242(4884), 1412-1415.
[http://dx.doi.org/10.1126/science.2849206] [PMID: 2849206]
[48]
Semenza, G.L.; Rue, E.A.; Iyer, N.V.; Pang, M.G.; Kearns, W.G. Assignment of the hypoxia-inducible factor 1α gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14q. Genomics, 1996, 34(3), 437-439.
[http://dx.doi.org/10.1006/geno.1996.0311] [PMID: 8786149]
[49]
Salnikow, K.; Kasprzak, K.S. Ascorbate depletion: a critical step in nickel carcinogenesis? Environ. Health Perspect., 2005, 113(5), 577-584.
[http://dx.doi.org/10.1289/ehp.7605] [PMID: 15866766]
[50]
Michiels, C. Physiological and pathological responses to hypoxia. Am. J. Pathol., 2004, 164(6), 1875-1882.
[http://dx.doi.org/10.1016/S0002-9440(10)63747-9] [PMID: 15161623]
[51]
Iyer, N.V.; Kotch, L.E.; Agani, F.; Leung, S.W.; Laughner, E.; Wenger, R.H.; Gassmann, M.; Gearhart, J.D.; Lawler, A.M.; Yu, A.Y.; Semenza, G.L. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 α. Genes Dev., 1998, 12(2), 149-162.
[http://dx.doi.org/10.1101/gad.12.2.149] [PMID: 9436976]
[52]
Hogenesch, J.B.; Chan, W.K.; Jackiw, V.H.; Brown, R.C.; Gu, Y.Z.; Pray-Grant, M.; Perdew, G.H.; Bradfield, C.A. Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J. Biol. Chem., 1997, 272(13), 8581-8593.
[http://dx.doi.org/10.1074/jbc.272.13.8581] [PMID: 9079689]
[53]
Ladoux, A.; Frelin, C. Cardiac expressions of HIF-1 α and HLF/EPAS, two basic loop helix/PAS domain transcription factors involved in adaptative responses to hypoxic stresses. Biochem. Biophys. Res. Commun., 1997, 240(3), 552-556.
[http://dx.doi.org/10.1006/bbrc.1997.7708] [PMID: 9398602]
[54]
Song, X.; Fiati Kenston, S.S.; Kong, L.; Zhao, J. Molecular mechanisms of nickel induced neurotoxicity and chemoprevention. Toxicology, 2017, 392, 47-54.
[http://dx.doi.org/10.1016/j.tox.2017.10.006] [PMID: 29032222]
[55]
He, M.; Lu, Y.; Xu, S.; Mao, L.; Zhang, L.; Duan, W.; Liu, C.; Pi, H.; Zhang, Y.; Zhong, M.; Yu, Z.; Zhou, Z. MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron-sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells. Cell Death Dis., 2014, 5(2) e1090
[http://dx.doi.org/10.1038/cddis.2014.60] [PMID: 24577088]
[56]
Viemann, D.; Schmidt, M.; Tenbrock, K.; Schmid, S.; Müller, V.; Klimmek, K.; Ludwig, S.; Roth, J.; Goebeler, M. The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J. Immunol., 2007, 178(5), 3198-3207.
[http://dx.doi.org/10.4049/jimmunol.178.5.3198] [PMID: 17312168]
[57]
Wani, S.A.; Khan, L.A.; Basir, S.F. Role of calcium channels and endothelial factors in nickel induced aortic hypercontraction in Wistar rats. J. Smooth Muscle Res., 2018, 54(0), 71-82.
[http://dx.doi.org/10.1540/jsmr.54.71] [PMID: 30210089]
[58]
Fu, Z.; Gilbert, E.R.; Liu, D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr. Diabetes Rev., 2013, 9(1), 25-53.
[http://dx.doi.org/10.2174/157339913804143225] [PMID: 22974359]
[59]
Das, K.K.; Das, S.N.; Ambekar, J.G. Hypoxia and Oxidative Stress: Cell Signaling Mechanisms and Protective Role of Vitamin C and Cilnidipine. In: Lipid Peroxidation: Inhibition; Effects and Mechanisms; Angel, Catala., Ed.; Nova Publishers, 2017; pp. 249-262.
[60]
Tikare, S.N.; Das Gupta, A.; Dhundasi, S.A.; Das, K.K. Effect of antioxidants L-ascorbic acid and alpha-tocopherol supplementation in nickel exposed hyperglycemic rats. J. Basic Clin. Physiol. Pharmacol., 2008, 19(2), 89-101.
[http://dx.doi.org/10.1515/JBCPP.2008.19.2.89] [PMID: 19024927]
[61]
Metzen, E.; Fandrey, J.; Jelkmann, W. Evidence against a major role for Ca2+ in hypoxia-induced gene expression in human hepatoma cells (Hep3B). J. Physiol., 1999, 517(Pt 3), 651-657.
[http://dx.doi.org/10.1111/j.1469-7793.1999.0651s.x] [PMID: 10358107]
[62]
Szarka, A.; Lőrincz, T. The role of ascorbate in protein folding. Protoplasma, 2014, 251(3), 489-497.
[http://dx.doi.org/10.1007/s00709-013-0560-5] [PMID: 24150425]
[63]
Myllylä, R.; Majamaa, K.; Günzler, V.; Hanauske-Abel, H.M.; Kivirikko, K.I. Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. J. Biol. Chem., 1984, 259(9), 5403-5405.
[PMID: 6325436]
[64]
Jacob, R.A.; Sotoudeh, G.; Vitamin, C. Vitamin C function and status in chronic disease. Nutr. Clin. Care, 2002, 5(2), 66-74.
[http://dx.doi.org/10.1046/j.1523-5408.2002.00005.x] [PMID: 12134712]
[65]
Frei, B.; England, L.; Ames, B.N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. USA, 1989, 86(16), 6377-6381.
[http://dx.doi.org/10.1073/pnas.86.16.6377] [PMID: 2762330]
[66]
Lehr, H.A.; Frei, B.; Olofsson, A.M.; Carew, T.E.; Arfors, K.E. Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E. Circulation, 1995, 91(5), 1525-1532.
[http://dx.doi.org/10.1161/01.CIR.91.5.1525] [PMID: 7867194]
[67]
Das, K.K.; Das, S.N. Studies on the role of ascorbic acid on nickel induced hepatic nucleic acid concentrations in rats. J. Basic Clin. Physiol. Pharmacol., 2004, 15(3-4), 185-195.
[http://dx.doi.org/10.1515/JBCPP.2004.15.3-4.185] [PMID: 15803957]
[68]
Hattiwale, S.H.; Saha, S.; Yendigeri, S.M.; Jargar, J.G.; Dhundasi, S.A.; Das, K.K. Protective effect of L-ascorbic acid on nickel induced pulmonary nitrosative stress in male albino rats. Biometals, 2013, 26(2), 329-336.
[http://dx.doi.org/10.1007/s10534-013-9617-3] [PMID: 23463385]
[69]
Das, K.K.; Saha, S. L-ascorbic acid and α tocopherol supplementation and antioxidant status in nickel- or lead-exposed rat brain tissue. J. Basic Clin. Physiol. Pharmacol., 2010, 21(4), 325-346.
[http://dx.doi.org/10.1515/JBCPP.2010.21.4.325] [PMID: 21305849]
[70]
Gupta, A.D.; Dhundasi, S.A.; Ambekar, J.G.; Das, K.K. Effect of l-ascorbic acid on antioxidant defense system in testes of albino rats exposed to nickel sulfate. J. Basic Clin. Physiol. Pharmacol., 2007, 18(4), 255-266.
[http://dx.doi.org/10.1515/JBCPP.2007.18.4.255] [PMID: 18380167]
[71]
Das, K.K.; Gupta, A.D.; Dhundasi, S.A.; Patil, A.M.; Das, S.N.; Ambekar, J.G. Protective role of L-ascorbic acid on antioxidant defense system in erythrocytes of albino rats exposed to nickel sulfate. Biometals, 2007, 20(2), 177-184.
[http://dx.doi.org/10.1007/s10534-006-9025-z] [PMID: 16900397]
[72]
Gupta, A.D.; Patil, A.M.; Ambekar, J.G.; Das, S.N.; Dhundasi, S.A.; Das, K.K. L-ascorbic acid protects the antioxidant defense system in nickel-exposed albino rat lung tissue. J. Basic Clin. Physiol. Pharmacol., 2006, 17(2), 87-100.
[http://dx.doi.org/10.1515/JBCPP.2006.17.2.87] [PMID: 16910314]
[73]
Das, K.K.; Gupta, A.D.; Dhundasi, S.A.; Patil, A.M.; Das, S.N.; Ambekar, J.G. Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats. J. Basic Clin. Physiol. Pharmacol., 2006, 17(1), 29-44.
[http://dx.doi.org/10.1515/JBCPP.2006.17.1.29] [PMID: 16639878]
[74]
Pandareesh, M.D.; Kandikattu, H.K.; Razack, S.; Amruta, N.; Choudhari, R.; Vikram, A.; Doddapattar, P. Nutrition and nutraceuticals in neuroinflammatory and brain metabolic stress: implications for neurodegenerative disorders. CNS Neurol. Disord. Drug Targets, 2018, 17(9), 680-688.
[http://dx.doi.org/10.2174/1871527317666180625104753] [PMID: 29938622]

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