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The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes.
Chem Biol Interact. 2015 Apr 25; 231:18-26.CB

Abstract

Oxidative stress is implicated in toxicant-induced inflammation leading to chronic diseases. Polymorphonuclear leukocytes (PMNs) offer the first line of defense against infection in the mammals and protect against inflammation-mediated pathological anomalies. Conversely, activated PMNs contribute to the oxidative stress-mediated damage and inflammation. The study aimed to investigate the status of oxidative stress and antioxidant defense system in the PMNs of rats treated with/without zinc (Zn) and/or paraquat (PQ) in the presence or absence of a synthetic superoxide dismutase/catalase mimetic, a manganese-salen compound-EUK-134 and/or a glutathione precursor, N-acetyl cysteine (NAC). While Zn and/or PQ elevated the total free radical generation, lipid peroxidation (LPO) and catalytic activity of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase alpha 4-4 (GSTA4-4), a pronounced decrease in reduced glutathione (GSH) and glutathione reductase (GR) activity was also observed. Zn and/or PQ augmented the expression of metallothionein-I and II and GSTA4-4. Pre-treatment of EUK-134 or NAC alone altered the level of total free radical generation, LPO, GSH content and catalytic activity of MPO, SOD, GR and GPx and the expression of metallothionein I and II towards normalcy. The alterations were more pronounced in the PMNs of rats treated with EUK-134 and NAC in combination. Catalytic activity/expression of GSTA4-4 remained unchanged in the PMNs of EUK-134 or NAC treated rats. The results demonstrate that EUK-134 and NAC protect PMNs from the toxic effects of Zn and PQ in rats and also suggest that metallothioneins I/II might contribute to antioxidant defense under GSH depleted conditions.

Authors+Show Affiliations

CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India.CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India.CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.Banaras Hindu University (BHU), Varanasi 221 005, UP, India.CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: singhchetnaitrc@rediffmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25724285

Citation

Kumar, Ashutosh, et al. "The Manganese-salen Compound EUK-134 and N-acetyl Cysteine Rescue From Zinc- and Paraquat-induced Toxicity in Rat Polymorphonuclear Leukocytes." Chemico-biological Interactions, vol. 231, 2015, pp. 18-26.
Kumar A, Shukla S, Chauhan AK, et al. The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes. Chem Biol Interact. 2015;231:18-26.
Kumar, A., Shukla, S., Chauhan, A. K., Singh, D., Pandey, H. P., & Singh, C. (2015). The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes. Chemico-biological Interactions, 231, 18-26. https://doi.org/10.1016/j.cbi.2015.02.012
Kumar A, et al. The Manganese-salen Compound EUK-134 and N-acetyl Cysteine Rescue From Zinc- and Paraquat-induced Toxicity in Rat Polymorphonuclear Leukocytes. Chem Biol Interact. 2015 Apr 25;231:18-26. PubMed PMID: 25724285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes. AU - Kumar,Ashutosh, AU - Shukla,Smriti, AU - Chauhan,Amit Kumar, AU - Singh,Deepali, AU - Pandey,Haushila Prasad, AU - Singh,Chetna, Y1 - 2015/02/24/ PY - 2014/07/14/received PY - 2015/02/02/revised PY - 2015/02/17/accepted PY - 2015/3/1/entrez PY - 2015/3/1/pubmed PY - 2015/6/17/medline KW - EUK-134 KW - NAC KW - Oxidative stress KW - Paraquat KW - Zinc SP - 18 EP - 26 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 231 N2 - Oxidative stress is implicated in toxicant-induced inflammation leading to chronic diseases. Polymorphonuclear leukocytes (PMNs) offer the first line of defense against infection in the mammals and protect against inflammation-mediated pathological anomalies. Conversely, activated PMNs contribute to the oxidative stress-mediated damage and inflammation. The study aimed to investigate the status of oxidative stress and antioxidant defense system in the PMNs of rats treated with/without zinc (Zn) and/or paraquat (PQ) in the presence or absence of a synthetic superoxide dismutase/catalase mimetic, a manganese-salen compound-EUK-134 and/or a glutathione precursor, N-acetyl cysteine (NAC). While Zn and/or PQ elevated the total free radical generation, lipid peroxidation (LPO) and catalytic activity of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase alpha 4-4 (GSTA4-4), a pronounced decrease in reduced glutathione (GSH) and glutathione reductase (GR) activity was also observed. Zn and/or PQ augmented the expression of metallothionein-I and II and GSTA4-4. Pre-treatment of EUK-134 or NAC alone altered the level of total free radical generation, LPO, GSH content and catalytic activity of MPO, SOD, GR and GPx and the expression of metallothionein I and II towards normalcy. The alterations were more pronounced in the PMNs of rats treated with EUK-134 and NAC in combination. Catalytic activity/expression of GSTA4-4 remained unchanged in the PMNs of EUK-134 or NAC treated rats. The results demonstrate that EUK-134 and NAC protect PMNs from the toxic effects of Zn and PQ in rats and also suggest that metallothioneins I/II might contribute to antioxidant defense under GSH depleted conditions. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/25724285/The_manganese_salen_compound_EUK_134_and_N_acetyl_cysteine_rescue_from_zinc__and_paraquat_induced_toxicity_in_rat_polymorphonuclear_leukocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(15)00074-5 DB - PRIME DP - Unbound Medicine ER -