Impact of pirimicarb on Neuro-immune-endocrine system sensitivity and the preventive effect of Ephedra alata monjauzeana.

Abstract

Pesticide users and manufacturers should anticipate exposure to toxicological risks, withal; the general public is not exempted. The use of carbamate insecticides poses a threat to human health, and pirimicarb is the most used carbamate. This research project sought to determine the impact of pirimicarb on the neuroimmune endocrine axis and to evaluate the eventual preventive ability of Ephedra alata monjauzeana. Preliminary in vitro and in vivo investigations were performed to assess the antioxidant, anti-inflammatory and the non-toxic effects of the prepared crude extract from the plant of interest. In addition, LCMS/MS qualitative analysis was conducted for the characterization of the chemical profile. Twenty‐one flavonoids and phenolic acids were identified in the EamCE, this latter exhibited a remarkable antioxidant activity and an interesting anti-inflammatory potential. The tests of toxicity and cytotoxicity indicated our plant as non-toxic and relatively harmless. Moreover, the pirimicarb noxiousness was determined by inducing a subacute toxicity on male wistar rats after a period of 28 days of pirimicarb daily gavage (1/10 of LD50 = 145 mg/kg). The exploration of the noxious effects was realized by various analysis. Behavioral tests were used to evaluate the mood and behavior changes and to estimate the physical performance. Oxidative stress was determined by analyzing some parameters, namely: MDA, GSH SOD and CAT. The measurement of inflammatory and hormonal biomarkers such as blood cells count, IL-1 β level, cortisol and testosterone serum titers were also carried. At the histologic scale, the significance of lesions was specifically examined in the brain and testis. In other respects, traces of pirimicarb in extracts of the same organs were searched using LCMS/MS MRM. Consequently, a considerable status of anxiety and depression was revealed, with a remarkable rise in cortisol, monocytes, IL-1 β (peripheral and cerebral) titers. Likewise, a significant decline in oxidative enzymes and testosterone rate as well as a status of lymphopenia and agranulocytosis were recorded. Additionally, important histological lesions were shown in cerebral cortex and seminiferous tubules. The chromatographic analysis of extracts amples from brain and testis of rats force-fed with pirimicarb provided accurately chromatograms that demonstrated the detection of pirimicarb and approved its accumulation in tissues. The EamCE showed exceptional promising results, as a preventive therapeutic agent, which is characterized by restoring mental and physical performances, enhancing mood, fertility, antioxidant and antiinflammatory activities, and maintaining tissue integrity. In further, we carried another test to confirm the cytotoxic effect of pirimicarb on immune cells where we used human blood cells from healthy donors, to separate neutrophils and reacting them with different concentrations and mixtures of pirimicarb and EamCE. Therefore, pirimicarb induced the reduction of neutrophils viability percentage, in contrast to the enhanced effect of EamCE. Overall, we believe that is pertinent to mention that EamCE possesses euphoric and preventive properties towards pirimicarb negative impacts that are manifested by disrupting the neuro-immune endocrine axis.