The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes.
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.
CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India.
Ashutosh
A
Kumar
CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India.
Smriti
S
Shukla
CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
Amit Kumar
AK
Chauhan
CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
Deepali
D
Singh
Banaras Hindu University (BHU), Varanasi 221 005, UP, India.
Haushila Prasad
HP
Pandey
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.
Chetna
C
Singh
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000633:toxicity*
D000975:Antioxidants; C433928:EUK-134; D006540:Herbicides; D007527:Isoenzymes; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012459:Salicylates; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D015032:Zinc; D010269:Paraquat; D000111:Acetylcysteine
EUK-134; NAC; Oxidative stress; Paraquat; Zinc