Herbicide Paraquat provokes the stress responses of HPA axis of laboratory mouse, Mus musculus.

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.

Hyperglycemia and high nitric oxide level induced oxidative stress in the brain and molecular alteration in the neurons and glial cells of laboratory mouse, Mus musculus.

Chronic hyperglycemia (glucotoxicity) is reported to have detrimental effects on various brain functions leading to neurodegenerative changes. However, the effect of hyperglycemia in combination with high nitric oxide (NO) level (reported to be increased during glucotoxicity), on brain functions is not clear yet. The present study was designed to investigate the effects of hyperglycemic drug Streptozotocin (STZ) and NO donor Sodium nitroprusside (SNP) on the brain of laboratory mouse, Mus musculus. Effects of these conditions were studied on the markers of oxidative stress, NF-κB signalling and the markers of neuronal and glial cell activation/inflammation. Results indicate increased level of MDA and altered antioxidant enzymes activity in both the treated groups compared to control but high levels of AGEs, AOPP and AR activity (markers of diabetic complications) were observed in STZ group only. On the other hand, while STZ group showed decreased IL-6 level, it was increased in SNP group but IFN-ϒ level increased in both the treated groups compared to control. Further, in addition to alterations in the expressions of iNOS, IKKß, IKBα and NF-κB subunits (RelA-p65/RelB-p50) observed in the neurons and glial cells of different brain regions (hypothalamus, basolateral amygdala and cerebral cortex), enhanced expression of microglial CD11b and astrocytic GFAP was also found in both the treated groups compared to control. Present findings led us to conclude that both hyperglycemia and high NO level causes oxidative stress in addition to molecular alteration in the neurons and glial cells. It is suggested that high blood glucose and NO level induced oxidative stress may lead to neuroinflammation possibly via NF-κB signalling.