Satpute R M, Pawar P P, Puttewar S, Sawale S D, Ambhore P D
1 Toxicology Laboratory, Defence Research and Development Establishment, Nagpur, Maharashtra, India.
2 Department of Biotechnology, S.F.S. College, Seminari Hills, Nagpur, India.
Hum Exp Toxicol. 2017 Dec;36(12):1303-1314. doi: 10.1177/0960327116688070. Epub 2017 Jan 16.
Paraquat (PQ) is a nonselective bipyridyl herbicide widely used in agriculture to control weeds, but its accidental, occupational, or intentional exposure in humans is known to cause pneumo- and neurotoxicity which may proves fatal. Oxidative stress is reported as an underlined mechanism of PQ-induced toxicity in alveolar cells, neurons, and astroglia. PQ generates superoxides both through electron transport reaction (ETC) with nicotinamide adenine dinucleotide-dependent oxidoreductase and by the redox cycling via reaction with molecular oxygen. In lungs, it causes edema and inflammation resulting in neutrophils infiltration and subsequent activation of pro-inflammatory cytokines. In the present study, toxicity of subacute oral PQ exposure and effect of resveratrol (Res) and/or tetracycline (TC) on oxidative stress and inflammatory markers in lungs, brain, and liver was studied. Levels of glutathione and malondialdehyde and activities of myeloperoxidase, glutathione peroxidase, and catalase were measured in lungs, brain, and liver. PQ interferes in the function of mitochondrial ETC complexes causing decreased adenosine triphosphate levels, and hence the activities of complexes I and IV were studied in brain tissues. Res, a natural antioxidant, and TC, an antibiotic with its antimicrobial and anti-inflammatory properties, offered significant protection from severe oxidative stress and inflammation and ameliorated the general well-being of mice against the toxic outcome of PQ.
百草枯（PQ）是一种非选择性联吡啶类除草剂，在农业中广泛用于控制杂草，但已知人类意外、职业性或故意接触百草枯会导致肺毒性和神经毒性，可能会致命。氧化应激被报道为百草枯在肺泡细胞、神经元和星形胶质细胞中诱导毒性的潜在机制。百草枯通过与烟酰胺腺嘌呤二核苷酸依赖性氧化还原酶的电子传递反应（ETC）以及与分子氧反应的氧化还原循环产生超氧化物。在肺部，它会导致水肿和炎症，导致中性粒细胞浸润以及随后促炎细胞因子的激活。在本研究中，研究了亚急性口服百草枯暴露的毒性以及白藜芦醇（Res）和/或四环素（TC）对肺、脑和肝脏中氧化应激和炎症标志物的影响。测量了肺、脑和肝脏中谷胱甘肽和丙二醛的水平以及髓过氧化物酶、谷胱甘肽过氧化物酶和过氧化氢酶的活性。百草枯干扰线粒体ETC复合物的功能，导致三磷酸腺苷水平降低，因此研究了脑组织中复合物I和IV的活性。白藜芦醇是一种天然抗氧化剂，四环素是一种具有抗菌和抗炎特性的抗生素，它们对严重的氧化应激和炎症提供了显著的保护，并改善了小鼠的总体健康状况，使其免受百草枯毒性后果的影响。
