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IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes.
Mol Cell Biochem. 2017 Mar; 427(1-2):133-143.MC

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.

Authors+Show Affiliations

Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India. Academy of Scientific and Innovative Research, CSIR-IITR Campus, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India.Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India. Academy of Scientific and Innovative Research, CSIR-IITR Campus, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India.Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India. chetna@iitr.res.in. Academy of Scientific and Innovative Research, CSIR-IITR Campus, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India. chetna@iitr.res.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28025796

Citation

Singh, Deepali, et al. "IFN-γ Regulates Xanthine Oxidase-mediated iNOS-independent Oxidative Stress in Maneb- and Paraquat-treated Rat Polymorphonuclear Leukocytes." Molecular and Cellular Biochemistry, vol. 427, no. 1-2, 2017, pp. 133-143.
Singh D, Kumar V, Singh C. IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes. Mol Cell Biochem. 2017;427(1-2):133-143.
Singh, D., Kumar, V., & Singh, C. (2017). IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes. Molecular and Cellular Biochemistry, 427(1-2), 133-143. https://doi.org/10.1007/s11010-016-2905-9
Singh D, Kumar V, Singh C. IFN-γ Regulates Xanthine Oxidase-mediated iNOS-independent Oxidative Stress in Maneb- and Paraquat-treated Rat Polymorphonuclear Leukocytes. Mol Cell Biochem. 2017;427(1-2):133-143. PubMed PMID: 28025796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IFN-γ regulates xanthine oxidase-mediated iNOS-independent oxidative stress in maneb- and paraquat-treated rat polymorphonuclear leukocytes. AU - Singh,Deepali, AU - Kumar,Vinod, AU - Singh,Chetna, Y1 - 2016/12/26/ PY - 2016/08/26/received PY - 2016/12/03/accepted PY - 2016/12/28/pubmed PY - 2017/2/18/medline PY - 2016/12/28/entrez KW - Cytokines KW - Maneb KW - Oxidative stress KW - Paraquat KW - Polymorphonuclear leukocytes KW - Xanthine oxidase SP - 133 EP - 143 JF - Molecular and cellular biochemistry JO - Mol Cell Biochem VL - 427 IS - 1-2 N2 - 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. SN - 1573-4919 UR - https://www.unboundmedicine.com/medline/citation/28025796/IFN_��_regulates_xanthine_oxidase_mediated_iNOS_independent_oxidative_stress_in_maneb__and_paraquat_treated_rat_polymorphonuclear_leukocytes_ L2 - https://doi.org/10.1007/s11010-016-2905-9 DB - PRIME DP - Unbound Medicine ER -