Vitamin B6 prevents Isocarbophos-induced posterior cerebral artery injury in offspring rats through up-regulating S1P receptor expression

Abstract

We have previously reported that the long-term exposure of Isocarbophos, a kind of organophosphorus compounds, induces vascular dementia (VD) in rats. Studies have also shown that organophosphorus compounds have adverse effects on offsprings. Vitamin B6 is a coenzyme mainly involved in the regulation of metabolism and has been demonstrated to ameliorate VD. Sphingosine-1-phosphate (S1P), a biologically active lipid, plays a vital role in the cardiovascular system. However, whether S1P is involved in the therapeutic effects of Vitamin B6 on posterior cerebral artery injury has yet to be further answered. In the present study, we aimed to explore the potential influence of Vitamin B6 on Isocarbophos-induced posterior cerebral artery injury in offspring rats and the role of the S1P receptor in this process. We found that Vitamin B6 significantly improves the vasoconstriction function of the posterior cerebral artery in rats induced by Isocarbophos by the blood gas analysis and endothelium-dependent relaxation function assay. We further demonstrated that Vitamin B6 alleviates the Isocarbophos-induced elevation of ICAM-1, VCAM-1, IL-1, and IL-6 by using the enzyme-linked immunosorbent assay kits. By performing immunofluorescence and the western blot assay, we revealed that Vitamin B6 prevents the down-regulation of S1P in posterior cerebral artery injury. It is worth noting that Fingolimod, the S1P inhibitor, significantly inhibits the Vitamin B6-induced up-regulation of S1P in posterior cerebral artery injury. Collectively, our data indicate that Vitamin B6 may be a novel drug for the treatment of posterior cerebral artery injury and that S1P may be a drug target for its treatment.

Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment

“…Vitamin B6 (VB6) can be used to prevent and treat lip splitting, seborrheic dermatitis, and diabetic vascular complications. In recent years, it has been found that VB6 can be used to prevent and treat CNS diseases (126). Li et al (127) used VB6 (50 mg/kg/d BW by gavage) to interfere with the vascular dementia model rats induced by isocarbophos (0.5 mg/kg/d BW by gavage) and found that VB6 could improve the behavior retardation and memory impairment.…”

Dissecting the Enantioselective Neurotoxicity of Isocarbophos: Chiral Insight from Cellular, Molecular, and Computational Investigations

“…Today, it is accepted that organophosphorus agents may exert their bioeffects by the inhibition of AChE, which leads to the accumulation of the neurotransmitter acetylcholine in synapses and overstimulates the postsynaptic cholinergic receptors with consequent signs of neurotoxicity. , Epidemiological survey results clarify that the adverse health effects (particularly neurotoxicity) of a great deal of residual organophosphorus pesticides on the human body are related closely to AChE. , In terms of isocarbophos, Li et al , disclosed that long-term low dose administration of isocarbophos to male Sprague-Dawley rats reduced the AChE activity in the hippocampus and the numbers of cholinergic neurons and injured primary neuronal cells, which could create cognitive impairment and cerebral arterial dysfunction and finally dementia (e.g., Alzheimer’s disease). Evidently, the in vivo rat bioassays suggest that the toxicological actions of isocarbophos on the typical mammalian model are mediated mainly by neuronal AChE, and isocarbophos can be considered as a neurotoxicant with high bioactivity to mammals including humans . Unfortunately, isocarbophos is a chiral pollutant, but its enantioselective neurotoxicity to mammalians remains unclear, and more importantly, the hidden mechanism behind isocarbophos-induced neurotoxicity is not decoded.…”

“…Evidently, the in vivo rat bioassays suggest that the toxicological actions of isocarbophos on the typical mammalian model are mediated mainly by neuronal AChE, and isocarbophos can be considered as a neurotoxicant with high bioactivity to mammals including humans. 52 Unfortunately, isocarbophos is a chiral pollutant, but its enantioselective neurotoxicity to mammalians remains unclear, and more importantly, the hidden mechanism behind isocarbophosinduced neurotoxicity is not decoded. Also, if the pioneering studies were unwrapped by in vivo assays, corresponding in vitro scrutinizations are essential to decrypt the results and phenomena in order to give the microscopic basis at the molecular/atomic scale to the understanding of the role of enantioselectivity.…”