Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Pestic Biochem Physiol. 2019 Jan;153:106-115. doi: 10.1016/j.pestbp.2018.11.008. Epub 2018 Nov 9.
Paraquat (PQ) is a herbicide and well characterized pneumotoxicant which is also known to induce neurodegeneration in organisms. Aim of this study was to investigate the effect of PQ on hypothalamic - pituitary - adrenal (HPA) axis. PQ was administered i.p.10 mg/kg body weight once a week for 5 weeks in laboratory male mice. Results indicate that SOD activity decreased while catalase activity and nitrate-nitrite level increased significantly in the hypothalamus of PQ treated mice. The expression of both AVP and CRH mRNA in the hypothalamus as well as ir-AVP and ir-CRH increased in the PVN of PQ treated mice compared to control. Immunoreactivity of nNOS and Hsp70 including NF-κB mRNA expression increased in the PVN of PQ treated mice. As expected, serum corticosterone level was also elevated significantly in the herbicide PQ treated mice. From these findings it is concluded that paraquat treatment is capable of activating the HPA axis via upregulating transcription and translation of the hypothalamic neuropeptides AVP and CRH as well as serum corticosterone level. Increase in both oxidative and nitrosative stress in PQ treated mice might be the driver which also contributed to the activation of HPA axis. It seems that stress induced reactive species (ROS, RNS) might be also responsible for the induced expression of NF-κB mRNA and Hsp70 protein which are considered as the reliable markers of certain types of stressors including PQ toxicity.
百草枯（PQ）是一种除草剂，也是一种特征明显的肺毒物，已知它还会导致生物的神经退行性变。本研究旨在研究 PQ 对下丘脑-垂体-肾上腺（HPA）轴的影响。将 PQ 以 10mg/kg 体重的剂量腹腔注射给药，每周一次，共 5 周，用于实验室雄性小鼠。结果表明，与对照组相比，PQ 处理的小鼠下丘脑的 SOD 活性降低，而过氧化氢酶活性和硝酸盐-亚硝酸盐水平显著升高。与对照组相比，下丘脑内 AVP 和 CRH mRNA 的表达以及 PVN 中的 ir-AVP 和 ir-CRH 增加。与对照组相比，PVN 中的 nNOS 和 Hsp70 的免疫反应性（包括 NF-κB mRNA 表达）增加。如预期的那样，除草剂 PQ 处理的小鼠血清皮质酮水平也显著升高。从这些发现可以得出结论，百草枯处理能够通过上调下丘脑神经肽 AVP 和 CRH 的转录和翻译以及血清皮质酮水平来激活 HPA 轴。PQ 处理的小鼠中氧化和硝化应激的增加可能是驱动 HPA 轴激活的原因。应激诱导的活性物质（ROS、RNS）可能也是诱导 NF-κB mRNA 和 Hsp70 蛋白表达的原因，这两种物质被认为是包括 PQ 毒性在内的某些类型应激源的可靠标志物。
