Functional impairment of blood-brain barrier following pesticide exposure during early development in rats.
1. The effect of certain pesticides on the functional integrity of the developing blood-brain barrier (BBB) was studied following single and repeated exposure, and after subsequent withdrawal in rats. 2. Ten-day-old rat pups exposed orally to quinalphos (QP, organophosphate), cypermethrin (CM, pyrethroid) and lindane (LD, organochlorine) at a dose of 1/50th of LD50, showed a significant increase in the brain uptake index (BUI) for a micromolecular tracer, sodium fluorescein (SF), by 97, 37 and 72%, respectively, after 2 h. Residual increases in the BUI were found even after 3 days of the single treatment of QP (28%) and LD (23%). 3. Repeated exposure for 8 days (postnatal days (PND) 10-17) with QP, CM and LD increased the BBB permeability by 130, 80 and 50%, respectively. Recovery from these changes was complete in QP and LD-treated animals after 13 days (PND 18-30) of withdrawal. However, CM showed persistent effects that were normalized only after 43 days (PND 18-60) of withdrawal. 4. A single dose reduced to 1/100th of LD50 also increased BUI in 10-day-old rat pups following QP (20%) and CM (28%) exposure at 2 h. 5. An age-dependent effect of these pesticides was evident from the study showing higher magnitude of BUI changes in 10-day-old rats as compared to that in 15-day-old rats. Furthermore, adult rats did not show any effect on BBB permeability even at a higher dose (1/25th of LD50) of these pesticides given alone or in combination with piperonyl butoxide (600 mg/kg, i.p.) for 3 consecutive days. 6. This study showed that developing BBB is highly vulnerable to single or repeated exposure of certain pesticides. The observed persistent effects during brain development even after withdrawal of the treatment may produce some neurological dysfunction at later life as well.
Gupta
A
A
Predictive Toxicology Research Group, Industrial Toxicology Research Centre, Lucknow, India.
Agarwal
R
R
Shukla
G S
GS
D000284:Administration, Oral; D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D005260:Female; D001556:Hexachlorocyclohexane / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D009946:Organothiophosphorus Compounds / Q000633:toxicity; D011247:Pregnancy; D011722:Pyrethrins / Q000633:toxicity; D051381:Rats
D007306:Insecticides; D009946:Organothiophosphorus Compounds; D011722:Pyrethrins; C017160:cypermethrin; C009145:quinalphos; D001556:Hexachlorocyclohexane