Molecular and Cellular Biochemistry

, Volume 427, Issue 1–2, pp 133–143 | Cite as

IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes

Article
First Online:
Received:
Accepted:

Abstract

Maneb (MB) and paraquat (PQ) provoke oxidative stress-mediated cell damage. Role of xanthine oxidase (XO) in oxidative stress and its association with nitric oxide (NO)/NO synthase (NOS) have been widely reported. While inducible NOS (iNOS) is implicated in MB+PQ-induced toxicity in rat polymorphonuclear leukocytes (PMNs), role of XO and its alliance with iNOS have not yet been established. The study investigated the role of XO in MB+PQ-induced oxidative stress in rat PMNs and its regulation by iNOS and inflammatory cytokines. MB+PQ-augmented reactive oxygen species (ROS), superoxide, nitro-tyrosine, lipid peroxidation (LPO), and nitrite levels along with the catalytic activity of iNOS, superoxide dismutase (SOD), and XO. XO inhibitor, allopurinol (AP), alleviated MB+PQ-induced changes except nitrite content and iNOS activity. Conversely, an iNOS inhibitor, aminoguanidine, mitigated MB+PQ-induced LPO, nitrite, iNOS, and nitro-tyrosine levels; however, no change was observed in ROS, SOD, and XO. Nuclear factor-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), tumor necrosis factor-alpha (TNF-α) inhibitor, pentoxyfylline, and an anti-inflammatory agent, dexamethasone, attenuated MB+PQ-induced increase in XO, superoxide, and ROS with parallel reduction in the expression of interferon-gamma (IFN-γ), TNF-α, and interleukin-1β (IL-1β) in rat PMNs. Exogenous IFN-γ, TNF-α, and IL-1β enhanced superoxide, ROS, and XO in the PMNs of control and MB+PQ-treated rats; however, IFN- γ was found to be the most potent inducer. Moreover, AP ameliorated cytokine-induced free radical generation and restored XO activity towards normalcy. The results thus demonstrate that XO mediates oxidative stress in MB+PQ-treated rat PMNs via iNOS-independent but cytokine (predominantly IFN-γ)-dependent mechanism.

Keywords

Maneb Paraquat Oxidative stress Xanthine oxidase Cytokines Polymorphonuclear leukocytes 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

Authors indisputably recognize the University Grants Commission (UGC), New Delhi, India and Department of Biotechnology (DBT), New Delhi, India for providing research fellowship to Deepali Singh and Vinod Kumar, respectively. The CSIR-IITR communication number of the article is 3412.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflicts of interest.

Research involving animal and human rights

The study was conducted after approval of Institutional Animal Ethics Committee. Additionally, the guidelines of the committee for the purpose of control and supervision of experiments on animals (CPCSEA) were stringently followed throughout the study.

References

  1. 1.
    Singh C, Ahmad I, Kumar A (2007) Pesticides and metals induced Parkinson’s disease: involvement of free radicals and oxidative stress. Cell Mol Biol 53:19–28PubMedGoogle Scholar
  2. 2.
    Blanco-Ayala T, Anderica-Romero AC, Pedraza-Chaverri J (2014) New insights into antioxidant strategies against paraquat toxicity. Free Radic Res 48:623–640CrossRefPubMedGoogle Scholar
  3. 3.
    Zhang J, Fitsanakis VA, Gu G, Jing D, Ao M, Amarnath V, Montine TJ (2003) Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: a link through mitochondrial dysfunction. J Neurochem 84:336–346CrossRefPubMedGoogle Scholar
  4. 4.
    Dixit A, Srivastava G, Verma D, Mishra M, Prakash O, Singh MP (2013) Minocycline, levodopa and MnTMPyP induced changes in the mitochondrial proteome profile of MPTP and maneb and paraquat mice models of Parkinson’s disease. Biochim Biophys Acta 1832:1227–1240CrossRefPubMedGoogle Scholar
  5. 5.
    Barlow BK, Thiruchelvam MJ, Bennice L, Cory-Slechta DA, Ballatori N, Richfield EK (2003) Increased synaptosomal dopamine content and brain concentration of paraquat produced by selective dithiocarbamates. J Neurochem 85:1075–1086CrossRefPubMedGoogle Scholar
  6. 6.
    Patel S, Singh V, Kumar A, Gupta YK, Singh MP (2006) Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb- and paraquat-induced Parkinson’s disease phenotype in mouse: mechanism of neurodegeneration. Brain Res 1081:9–18CrossRefPubMedGoogle Scholar
  7. 7.
    Domico LM, Zeevalk GD, Bernard LP, Cooper KR (2006) Acute neurotoxic effects of mancozeb and maneb in mesencephalic neuronal cultures are associated with mitochondrial dysfunction. Neurotoxicology 27:816–825CrossRefPubMedGoogle Scholar
  8. 8.
    Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20:1126–1167CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sawyer DW, Donowitz GR, Mandell GL (1989) Polymorphonuclear neutrophils: an effective antimicrobial force. Rev Infect Dis 11:1532–1544CrossRefGoogle Scholar
  10. 10.
    Ahmad I, Kumar A, Shukla S, Pandey HP, Singh C (2008) The involvement of nitric oxide in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes. Free Radic Res 42:849–862CrossRefPubMedGoogle Scholar
  11. 11.
    Tripathi P, Singh A, Agrawal S, Prakash O, Singh MP (2014) Cypermethrin alters the status of oxidative stress in the peripheral blood: relevance to Parkinsonism. J Physiol Biochem 70:915–924CrossRefPubMedGoogle Scholar
  12. 12.
    Kumar A, Shukla S, Chauhan AK, Singh D, Pandey HP, Singh C (2015) The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes. Chem Biol Interact 231:18–26CrossRefPubMedGoogle Scholar
  13. 13.
    Ahmad I, Shukla S, Singh D, Chauhan AK, Kumar V, Singh BK, Patel DK, Pandey HP, Singh C (2014) CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes. Mol Cell Biochem 393:209–222CrossRefPubMedGoogle Scholar
  14. 14.
    Shukla S, Singh D, Kumar V, Chauhan AK, Singh S, Ahmad I, Pandey HP, Singh C (2015) NADPH oxidase mediated maneb- and paraquat-induced oxidative stress in rat polymorphs: crosstalk with mitochondrial dysfunction. Pestic Biochem Physiol 123:74–86CrossRefPubMedGoogle Scholar
  15. 15.
    Ekelund UEG, Harrison RW, Shokek O, Thakkar RN, Tunin RS, Senzaki H, Kass DA, Marbán E, Hare JM (1999) Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure. Circ Res 85:437–445CrossRefPubMedGoogle Scholar
  16. 16.
    Romagnoli M, Gomez-Cabrera MC, Perrelli MG, Biasi F, Pallardo FV, Sastre J, Poli G, Vina J (2010) Xanthine oxidase-induced oxidative stress causes activation of NF-κB and inflammation in the liver of type I diabetic rats. Free Radic Biol Med 49:171–177CrossRefPubMedGoogle Scholar
  17. 17.
    Zhang JW, Lv GC, Zhao Y (2010) The significance of the measurement of serum xanthine oxidase and oxidation markers in patients with acute organophosphorus pesticide poisoning. J Int Med Res 38:458–465CrossRefPubMedGoogle Scholar
  18. 18.
    Kitazawa YM, Matsubara NT, Tanaka T (1991) The role of xanthine oxidase in paraquat intoxication. Arch Biochem Biophys 288:220–224CrossRefPubMedGoogle Scholar
  19. 19.
    Domico LM, Cooper KR, Bernard LP, Zeevalk GD (2007) Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells. Neurotoxicology 28:1079–1091CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gondouin B, Jourde-Chiche N, Sallee M, Dou L, Cerini C, Loundou A, Morange S, Berland Y, Burtey S, Brunet P, Guieu R, Dussol B (2015) Plasma xanthine oxidase activity is predictive of cardiovascular disease in patients with chronic kidney disease, independently of uric acid levels. Nephron 131:167–174CrossRefPubMedGoogle Scholar
  21. 21.
    MacIsaac RL, Salatzki J, Higgins P, Walters MR, Padmanabhan S, Dominiczak AF, Touyz RM, Dawson J (2016) Allopurinol and cardiovascular outcomes in adults with hypertension. Hypertension 67:535–540PubMedGoogle Scholar
  22. 22.
    Khan SK, Lee K, Minhas KM, Gonzalez DR, Raju SV, Tejani AD, Li D, Berkowitz DE, Hare JM (2004) Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase inhibition of cardiac excitation-contraction coupling. Proc Natl Acad Sci USA 101:15944–15948CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kinugawa S, Huang H, Wang Z, Kaminski PM, Wolin MS, Hintze TH (2005) A defect of neuronal nitric oxide synthase increases xanthine oxidase-derived superoxide anion and attenuates the control of myocardial oxygen consumption by nitric oxide derived from endothelial nitric oxide synthase. Circ Res 96:355–362CrossRefPubMedGoogle Scholar
  24. 24.
    Komaki Y, Sugiura H, Koarai A, Tomaki M, Ogawa H, Akita T, Hattori T, Ichinose M (2005) Cytokine-mediated xanthine oxidase up regulation in chronic obstructive pulmonary disease’s airways. Pulm Pharmacol Ther 18:297–302CrossRefPubMedGoogle Scholar
  25. 25.
    Singhal NK, Chauhan AK, Jain SK, Shanker R, Singh C, Singh MP (2013) Silymarin- and melatonin-mediated changes in the expression of selected genes in pesticides-induced Parkinsonism. Mol Cell Biochem 384:47–58CrossRefPubMedGoogle Scholar
  26. 26.
    Gupta SP, Patel S, Yadav S, Singh AK, Singh S, Singh MP (2010) Involvement of nitric oxide in maneb- and paraquat-induced Parkinson’s disease phenotype in mouse: is there any link with lipid peroxidation? Neurochem Res 35:1206–1213CrossRefPubMedGoogle Scholar
  27. 27.
    Ahmad I, Shukla S, Kumar A, Singh BK, Kumar V, Chauhan AK, Singh D, Pandey HP, Singh C (2013) Biochemical and molecular mechanisms of N-acetyl cysteine and siymarin-mediated protection against maneb- and paraquat-induced hepatotoxicity in rats. Chem Biol Interact 201:9–18CrossRefPubMedGoogle Scholar
  28. 28.
    Berisha H, Pakbaz H, Absood A, Foda HD, Said SI (1994) Nitric oxide mediates oxidant tissue injury caused by paraquat and xanthine oxidase. Ann NY Acad Sci 723:422–425CrossRefPubMedGoogle Scholar
  29. 29.
    Maqbool M, Vidyadaran S, George E, Ramasamy R (2011) Optimization of laboratory procedures for isolating human peripheral blood derived neutrophils. Med J Malays 66:296–299Google Scholar
  30. 30.
    Singh BK, Kumar V, Chauhan AK, Dwivedi A, Singh S, Kumar A, Singh D, Patel DK, Ray RS, Jain SK, Singh C (2016) Neuronal nitric oxide synthase negatively regulates zinc-induced nigrostriatal dopaminergic neurodegeneration. Mol Neurobiol. doi: 10.1007/s12035-016-9857-7 Google Scholar
  31. 31.
    Bradford MA (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMedGoogle Scholar
  32. 32.
    Roede J, Hansen MH, Go YM, Jones DP (2011) Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. Toxicol Sci 121:368–375CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ahmad I, Shukla S, Kumar A, Singh BK, Patel DK, Pandey HP, Singh C (2010) Maneb and paraquat-induced modulation of toxicant responsive genes in the rat liver: comparison with polymorphonuclear leukocytes. Chem Biol Interact 188:566–579CrossRefPubMedGoogle Scholar
  34. 34.
    Weidinger A, Kozlov AV (2015) Biological activities of reactive oxygen and nitrogen species: oxidative stress versus signal transduction. Biomolecules 5:472–484CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Chauhan AK, Mittra N, Kumar V, Patel DK, Singh C (2015) Inflammation and B-cell lymphoma-2 associated X protein regulate zinc-induced apoptotic degeneration of rat nigrostriatal dopaminergic neurons. Mol Neurobiol. doi: 10.1007/s12035-015-9478-6 Google Scholar
  36. 36.
    Dupont GP, Huecksteadt TP, Marshall BC, Ryan US, Michael JR, Hoidal JR (1992) Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. J Clin Investig 89:197–202CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Page S, Powell D, Benboubetra M, Stevens CR, Blake DR, Selase F, Wolstenholme AJ, Harrison R (1998) Xanthine oxidoreductase in human mammary epithelial cells: activation in response to inflammatory cytokines. Biochim Biophys Acta 1381:191–202CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment GroupCSIR-Indian Institute of Toxicology Research (CSIR-IITR)LucknowIndia
  2. 2.Academy of Scientific and Innovative ResearchCSIR-IITR CampusLucknowIndia

Personalised recommendations