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Effect of L-Ascorbic Acid on Nickel-Induced Alteration of Cardiovascular Pathophysiology in Wistar Rats

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Abstract

Nickel, a widely used heavy metal is suspected as a cardiotoxic element. The aim of the present study was to assess the possible protective role of l-ascorbic acid on nickel-induced alterations of cardiovascular pathophysiology in male albino rats. Twenty-four albino rats (b.wt. 170–250 g) were randomized into four groups: control; l-ascorbic acid (50 mg/100 g b.wt., orally); NiSO4 (2.0 mg/100 g b.wt., i.p.); NiSO4 with l-ascorbic acid. Cardiovascular electrophysiology, serum and cardiac tissue malondialdehyde (MDA), nitric oxide (NO), ascorbic acid, serum α-tocopherol and serum vascular endothelial growth factor (VEGF) were evaluated. Histopathology of cardiac and aortic tissues was also assessed. NiSO4-treated rats showed a significant increase in heart rate, LF/HF ratio and blood pressure (SBP, DBP and MAP). A significant increase of serum MDA, NO and VEGF in NiSO4 treatment with a concomitant decrease of serum ascorbic acid and α-tocopherol as compared to their respective controls were also observed. Simultaneous supplementation of l-ascorbic acid with NiSO4 significantly decreased LF/HF ratio, BP and oxidative stress parameters, whereas ascorbic acid and α-tocopherol concentration was found to be increased. Histopathology of cardiac and aortic tissues showed nickel-induced focal myocardial hypertrophy and degeneration in cardiac tissue with focal aneurism in aortic tissues. Supplementation with l-ascorbic showed a protective action in both cardiac and aortic tissues. Results indicated the possible beneficial effect of l-ascorbic acid on nickel-induced alteration of the cardiovascular pathophysiology in experimental rats.

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References

  1. Lippmann M, Ito K, Hwang JS et al (2006) Cardiovascular effects of nickel in ambient air. Environ Health Perspect 114:1662–1669. https://doi.org/10.1289/ehp.9150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang Z, Chau PYK, Lai HK, Wong CM (2009) A review of effects of particulate matter-associated nickel and vanadium species on cardiovascular and respiratory systems. Int J Environ Health Res 19:175–185. https://doi.org/10.1080/09603120802460392

    Article  CAS  PubMed  Google Scholar 

  3. Cosselman KE, Navas-Acien A, Kaufman JD (2015) Environmental factors in cardiovascular disease. Nat Rev Cardiol 12:627–642. https://doi.org/10.1038/nrcardio.2015.152

    Article  CAS  PubMed  Google Scholar 

  4. Vallejo M, Ruiz S, Hermosillo AG et al (2006) Ambient fine particles modify heart rate variability in young healthy adults. J Expo Sci Environ Epidemiol 16:125–130. https://doi.org/10.1038/sj.jea.7500447

    Article  CAS  PubMed  Google Scholar 

  5. Gold DR, Litonjua A, Schwartz J et al (2000) Ambient pollution and heart rate variability. Circulation 101:1267–1273

    Article  CAS  Google Scholar 

  6. Barceloux DG, Barceloux D (1999) Nickel. J Toxicol Clin Toxicol 37:239–258. https://doi.org/10.1081/CLT-100102423

    Article  CAS  PubMed  Google Scholar 

  7. Das KK, Dasgupta S (1997) Alteration of testicular biochemistry during protein restriction in nickel treated rats. Biol Trace Elem Res 60:243–249. https://doi.org/10.1007/BF02784444

    Article  CAS  PubMed  Google Scholar 

  8. Nielsen FH (1980) Effect of form of iron on the interaction between nickel and iron in rats: growth and blood parameters. J Nutr 110:965–973. https://doi.org/10.1093/jn/110.5.965

    Article  CAS  PubMed  Google Scholar 

  9. Sunderman FW, Hopfer SM, Sweeney KR et al (1989) Nickel absorption and kinetics in human volunteers. Proc Soc Exp Biol Med 191:5–11

    Article  CAS  Google Scholar 

  10. Das KK, Reddy RC, Bagoji IB et al (2019) Primary concept of nickel toxicity—an overview. J Basic Clin Physiol Pharmacol 30:141–152. https://doi.org/10.1515/jbcpp-2017-0171

    Article  CAS  Google Scholar 

  11. Wani SA, Khan LA, Basir SF (2018) Role of calcium channels and endothelial factors in nickel induced aortic hypercontraction in Wistar rats. J Smooth Muscle Res 54:71–82. https://doi.org/10.1540/jsmr.54.71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Niki E (1987) Interaction of ascorbate and a-tocopherol. Ann N Y Acad Sci 498:186–199

    Article  CAS  Google Scholar 

  13. Jargar JG, Yendigeri S, Dhundasi SA, Das KK (2014) Protective effect of vitamin E (a-tocopherol) on nickel-induced alteration of testicular pathophysiology in alloxan-treated diabetic rats. Int J Clin Exp Physiol 1:290. https://doi.org/10.4103/2348-8093.149762

  14. Das KK, Das SN, Dasgupta S (2001) The influence of ascorbic acid on nickel-induced hepatic lipid peroxidation in rats. J Basic Clin Physiol Pharmacol 12:187–195. https://doi.org/10.1515/JBCPP.2001.12.3.187

  15. Das KK, Dasgupta S (2002) Effect of nickel sulfate on testicular steroidogenesis in rats during protein restriction. Environ Health Perspect 110:923–926. https://doi.org/10.1289/ehp.02110923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Husain K, Sugendran K, Pant SC et al (1992) Biochemical and pathological changes in response to hyperoxia and protection by antioxidants in rats. Indian J Physiol Pharmacol 36:97–100

    CAS  PubMed  Google Scholar 

  17. Borders EPV (1983) Myocardial changes induced by nickel as in association with cadmium. Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol 32:51–56

    Google Scholar 

  18. Kawahara Y, Tanonaka K, Daicho T et al (2005) Preferable anesthetic conditions for echocardiographic determination of murine cardiac function. J Pharmacol Sci 99:95–104. https://doi.org/10.1254/jphs.FP0050343

    Article  CAS  PubMed  Google Scholar 

  19. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. https://doi.org/10.1016/S0076-6879(78)52032-6

    Article  CAS  PubMed  Google Scholar 

  20. Mohamed AA, Mubarak AT, Fawy KF, El-Shahat MF (2008) Modification of AOAC method 973.31 for determination of nitrite in cured meats. J AOAC Int 91:820–827

    Article  CAS  Google Scholar 

  21. Moshage H, Kok B, Huizenga JR, Jansen PLM (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 41:892–896. https://doi.org/10.1016/S0584-8547(97)00141-9

    Article  CAS  PubMed  Google Scholar 

  22. Roe JH, Kuether CA (1943) The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem 147:399–407

    CAS  Google Scholar 

  23. Jargar JG, Hattiwale SH, Das S et al (2012) A modified simple method for determination of serum α-tocopherol (vitamin E). J Basic Clin Physiol Pharmacol 23:45–48. https://doi.org/10.1515/jbcpp-2011-0033

    Article  CAS  PubMed  Google Scholar 

  24. Drury RAB (1986) Cellular pathology technique. J Clin Pathol 39:467–468

    Article  Google Scholar 

  25. Bray GA (2000) Reciprocal relation of food intake and sympathetic activity: experimental observations and clinical implications. Int J Obes Relat Metab Disord 24(Suppl 2):S8–S17

    Article  CAS  Google Scholar 

  26. Hunter JJ, Chien KR (1999) Signaling pathways for cardiac hypertrophy and failure. N Engl J Med 341:1276–1283. https://doi.org/10.1056/NEJM199910213411706

    Article  CAS  PubMed  Google Scholar 

  27. Julian RJ (2007) The response of the heart and pulmonary arteries to hypoxia, pressure, and volume. A short review. Poult Sci 86:1006–1011. https://doi.org/10.1093/ps/86.5.1006

    Article  CAS  PubMed  Google Scholar 

  28. Chuang H-C, Hsueh T-W, Chang C-C et al (2013) Nickel-regulated heart rate variability: the roles of oxidative stress and inflammation. Toxicol Appl Pharmacol 266:298–306. https://doi.org/10.1016/J.TAAP.2012.11.006

    Article  CAS  PubMed  Google Scholar 

  29. Kasprzak K (2003) Nickel carcinogenesis. Mutat Res Mol Mech Mutagen 533:67–97. https://doi.org/10.1016/j.mrfmmm.2003.08.021

    Article  CAS  Google Scholar 

  30. Koller A, Rubányi G, Ligeti L, Kovách AG (1982) Effect of verapamil and phenoxybenzamine on nickel-induced coronary vasoconstriction in the anaesthetized dog. Acta Physiol Acad Sci Hung 59:287–290

    CAS  PubMed  Google Scholar 

  31. Golovko VA, Bojtsov IV, Kotov LN (2003) Single and multiple early afterdepolarization caused by nickel in rat atrial muscle. Gen Physiol Biophys 22:275–278

    CAS  PubMed  Google Scholar 

  32. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837. https://doi.org/10.1093/eurheartj/ehr304

    Article  CAS  PubMed  Google Scholar 

  33. Das KK, Das SN, Dhundasi SA (2010) Nickel: molecular diversity, application, essentiality and toxicity in human health. In: Biometals: molecular structures, binding properties and applications. Nova Science Publishers Inc, pp 33–58

  34. Detmar M, Brown LF, Berse B et al (1997) Hypoxia regulates the expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptors in human skin. J Invest Dermatol 108:263–268. https://doi.org/10.1111/1523-1747.ep12286453

    Article  CAS  PubMed  Google Scholar 

  35. Hattiwale SH, Saha S, Yendigeri SM et al (2013) Protective effect of L-ascorbic acid on nickel induced pulmonary nitrosative stress in male albino rats. Biometals 26:329–336. https://doi.org/10.1007/s10534-013-9617-3

    Article  CAS  PubMed  Google Scholar 

  36. Pautz A, Art J, Hahn S et al (2010) Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23:75–93. https://doi.org/10.1016/j.niox.2010.04.007

    Article  CAS  PubMed  Google Scholar 

  37. Das KK, Honnutagi R, Mullur L et al (2019) Heavy metals and low-oxygen microenvironment—its impact on liver metabolism and dietary supplementation. In: Dietary interventions in liver disease. Elsevier, pp 315–332

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Funding

The first (RCR) and the last (KKD) author acknowledge the financial support from the Life Sciences Research Board (LSRB), Defence Research and Development Organisation (DRDO), Ministry of Defence, Government of India [R&D/81/48222/LSRB-285/EPB/2014 dated 18 July 2014], VGST (VGST-KFIST/1230/2015-16 dated 22 Jun 2016), Government of Karnataka, India.

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Authors and Affiliations

  1. Department of Biochemistry, Shri B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, Karnataka, 586103, India

    R. Chandramouli Reddy & Basavaraj Devaranavadagi

  2. Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, Karnataka, 586103, India

    R. Chandramouli Reddy, Shrilaxmi Bagali & Kusal K. Das

  3. Department of Pathology, Al-Ameen Medical College, Vijayapura, Karnataka, 586108, India

    Saeed M. Yendigeri

  4. Department of Pharmaceutics & Pharmaceutical Technology, BLDEA’s SSM College of Pharmacy & Research Centre, BLDE University Campus, Vijayapura, 586103, India

    Raghavendra V. Kulkarni

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  1. R. Chandramouli Reddy
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  2. Basavaraj Devaranavadagi
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  6. Kusal K. Das
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Correspondence to Kusal K. Das.

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Ethical Approval

Institutional Animal Ethical Committee (IAEC) approval was taken from BLDE Association’s Shri Sanganabasava Mahaswamiji College of Pharmacy & Research Centre, BLDE (Deemed to be University), Vijayapur, Karnataka, India (Ref No: BLDE/BPC/641/2016-2017 dated 22 October 2016) as per institutional CPCSEA (Committee for the Purpose of Control and Supervision of |Experiments on Animals), Ministry of Environment, Forests and Climate Change, Government of India Reg. No. 1076/PO/ERs/S/07 CPCSEA dated 20 August 2014.

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Reddy, R.C., Devaranavadagi, B., Yendigeri, S.M. et al. Effect of L-Ascorbic Acid on Nickel-Induced Alteration of Cardiovascular Pathophysiology in Wistar Rats. Biol Trace Elem Res 195, 178–186 (2020). https://doi.org/10.1007/s12011-019-01829-w

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