Effect of quinalphos and cypermethrin exposure on developing blood–brain barrier: role of nitric oxide

Abstract

Effect of low-level exposure of quinalphos (QP) and cypermethrin (CP) on the blood–brain barrier (BBB) permeability to macromolecular tracers, Evans blue (EB) and horseradish peroxidase (HRP) was studied in developing rat pups. Ten-day-old rat pups were daily exposed to QP and CP at a dose of ≈1/50th of adult LD50 through oral intubation, upto postnatal day 17 (PND). Functional integrity of the BBB was assessed by measuring the brain uptake index (BUI) of HRP and by visually grading the brains of control and treated rat pups for the staining of EB. Our results have demonstrated a significant increase in the BUI for HRP (204 and 254%) and have also shown a significant amount of EB staining in QP and CP exposed brains, respectively, as compared to the age-matched controls. Studies carried out with the nitric oxide synthase (NOS) inhibitor l-NAME (30 mg/kg, i.p., on alternate days from PND 10–17) have provided significant protection against the QP-induced increase in the BBB permeability, suggesting the possible involvement of NO in the barrier disruption. Microvessel acetylcholinesterase activity was also inhibited (53%, P<0.001) in QP-exposed rat pups only, with no change observed in CP-exposed microvessels. However, membrane fluidity was found to be decreased in both QP (18%, P<0.05) and CP (15%, P<0.05) exposed microvessels compared to controls. It is evident from the study that QP and CP exposure during early postnatal period causes significant impairment in the development and maturation of the BBB that may have adverse consequences on the normal brain functioning with long-term neurotoxic effects.