The involvement of nitric oxide in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes

Abstract

Oxidative stress plays a crucial role in the manifestations of maneb (MB) and paraquat (PQ)-induced toxicity including MB+PQ-induced Parkinson's disease (PD). Polymorphonuclear leukocytes (PMNs) actively participate in the oxidative stress-mediated inflammation and organ toxicity. The present study was undertaken to investigate the MB- and/or PQ-induced alterations in the indices of oxidative stress in rat PMNs. Animals were treated with or without MB and/or PQ in an exposure time dependent manner. In some sets of experiments, the animals were pre-treated with NOS inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) along with respective controls. A significant increase in myeloperoxidase (MPO), superoxide dismutase (SOD), nitric oxide, iNOS expression and lipid peroxidation (LPO) was observed in PMNs of MB- and/or PQ-treated animals, while catalase and glutathione S-transferase (GST) activities were attenuated. L-NAME and AG significantly reduced the augmented nitrite content, iNOS expression and MPO activity to control level in MB and PQ exposed animals. Although the augmented LPO was also reduced significantly in L-NAME and AG treated rat PMNs, the level was still higher as compared with controls. Alterations induced in SOD and GST activities were not affected by NOS inhibitors. The results thus suggest that MB and/or PQ induce iNOS-mediated nitric oxide production, which in turn increases MPO activity and lipid peroxidation, thereby oxidative stress.

Atorvastatin protected from paraquat-induced cytotoxicity in alveolar macrophages via down-regulation of TLR-4

“…Our findings demonstrate a positive correlation between the PQ-induced NO production and also MPO elevation by the PQ-exposed AMs, confirming the crucial role of NO in the activation of macrophages to produce MPO for further steps of inflammation (Pires et al, 2012). There is another report indicating the protective effect of L-NAME on the PQ-induced MPO activity in rat polymorphonuclear leukocytes, supporting the pathway that PQ induces the NO production and consequently enhances the MPO activities (Ahmad et al, 2008).…”

Nitric oxide in paraquat‐mediated toxicity: A review

“…iNOS mRNA is upregulated in vivo in rodents after administered PQ reaches significant levels in liver tissues, whereas kidney and lung tissues show little change [22,23]. Polymorphonuclear leukocytes (PMNs) isolated from rats exposed to PQ [24] and immortalized mesencephalic cells [25] also express iNOS. Human lung epithelial cells treated with PQ also express significant amounts of iNOS mRNA [23].…”

Medical management of paraquat ingestion

“…NO . is enzymatically produced from L‐arginine by NO synthase, and PQ also directly or indirectly induces NO synthase‐mediated nitric oxide production [23]. Generation of highly reactive oxygen and nitrite species results in toxicity in most organs but the toxicity is particularly severe in the lungs as paraquat is taken up against a concentration gradient in to the lung [24].…”