Immune-toxicity effects of scorpion venom on the hypothalamic pituitary adrenal axis during rest and activity phases in a rodent model

Abstract

Scorpion venom is a complex mixture of peptides and proteins, rich in toxins. Its toxicological effects are related to central disruptions and autonomic disturbances, organ failure, as well as an excessive systemic inflammatory response. Since the role of the hypothalamic pituitary adrenal (HPA) axis is central in the neuroendocrine-immunological axis, the purpose of this study was, therefore, to examine the immunotoxic effect of Androctonus australis hector (Aah) venom on HPA-axis in synchronised-mice model. Taking into account the circadian activity of the HPA-axis, the variations of adrenocorticotropic hormone and corticosterone plasma levels, oxidative stress as well as inflammatory markers in cerebral, hypothalamic and adrenal tissue homogenates were investigated during the rest and activity phases of animals. Histopathology study was also performed. Results showed that Aah venom activated the HPA axis. This response seems to be dependent on time of envenomation, as a higher hormone levels were more operative during the active phase than in the rest phase when compared to time-matched control. The local toxicity-effects following Aah envenomation revealed an imbalance in oxidative stress with a higher antioxidant defences in darkness hypothalamic and cerebral tissues. Furthermore, there were significantly higher levels in vascular permeability in hypothalamic and cerebral tissues accompanied by a concomitant increase in immune-cell infiltration and/or activation as shown by expression of CD68 and myeloperoxidase activity during the active phase compared with the rest phase. Overall results suggested that Aah venom had a toxic impact on different HPA-axis areas and the effect varies according to the time of envenomation.