NADPH oxidase mediated maneb- and paraquat-induced oxidative stress in rat polymorphs: Crosstalk with mitochondrial dysfunction.
Oxidative stress is a key factor in Parkinson's disease (PD) pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and impaired mitochondrion regulate oxidative stress-mediated maneb (MB)- and paraquat (PQ)-induced Parkinsonism. However, their contribution in the MB- and PQ-induced toxicity in polymorphonuclear leukocytes (PMNs) is still elusive. The study investigated the role of NADPH oxidase and mitochondria in MB- and/or PQ-induced oxidative stress in the PMNs and the crossing point between the two. Animals were treated with MB and/or PQ for 1-3 weeks along with respective controls. In a few sets of experiments, rats were treated with/without NADPH oxidase inhibitor, apocynin, an hour prior to MB and/or PQ treatment. PMNs of MB and/or PQ treated animals were also treated with/without carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to assess the role of the mitochondria in superoxide and total free radical productions. MB and/or PQ were found to increase the level of total reactive oxygen species (ROS), superoxide radicals, catalytic activity and expression of NADPH oxidase and superoxide dismutase (SOD1/2) and mitochondrial ROS content in a time dependent manner. Conversely, catalase activity and mitochondrial membrane potential were attenuated. Apocynin alleviated MB- and/or PQ-induced changes in total ROS, superoxide radicals, expression/catalytic activity of NADPH oxidase and SOD1/2 along with the mitochondrial ROS and membrane potential. CCCP also inhibited ROS and superoxide levels in the PMNs of MB and/or PQ-treated animals. The results demonstrate the involvement of NADPH oxidase and mitochondrial dysfunction in MB and PQ-induced oxidative stress in PMNs and a plausible crosstalk between them.
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India.
Smriti
S
Shukla
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), India.
Deepali
D
Singh
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), India.
Vinod
V
Kumar
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), India.
Amit Kumar
AK
Chauhan
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India.
Shweta
S
Singh
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India.
Israr
I
Ahmad
Banaras Hindu University, Varanasi 221 005, Uttar Pradesh, India.
Haushila Prasad
HP
Pandey
CSIR-Indian Institute of Toxicology Research, Lucknow 226 001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), India. Electronic address: singhchetnaitrc@rediffmail.com.
Chetna
C
Singh
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000633:toxicity; D006540:Herbicides / Q000633:toxicity; D008344:Maneb / Q000633:toxicity; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000098:Acetophenones; D004791:Enzyme Inhibitors; D005659:Fungicides, Industrial; D006540:Herbicides; D017382:Reactive Oxygen Species; D008344:Maneb; C056165:acetovanillone; D019255:NADPH Oxidases; D010269:Paraquat
Maneb; Mitochondrial dysfunction; NADPH oxidase; Oxidative stress; Paraquat