TRIAZOPHOS BIOACCUMULATION IN RAT BRAIN: ASSOCIATION WITH BLOOD–BRAIN BARRIER TRANSPORTER DYSREGULATION AND OXIDATIVE STRESS

Abstract

Triazophos (TZ), a broad-spectrum organophosphate pesticide that inhibits acetylcholinesterase enzyme (AChE), is highly toxic to nontarget species through contaminated water and food. In the present study, male Wistar rats were exposed to 8.2 mg/kg TZ (1/10th of oral LD50) for 30 days, and brain tissues were assessed for (a) the gene expression of membrane transporters of blood–brain barrier (BBB) viz., organic anion transporter protein (OATP2) and P-glycoprotein (PGP) via real-time PCR and immunohistochemistry (IHC), (b) oxidative damage and (c) subsequent bioaccumulation in blood and brain tissues via LC‒MS, respectively. Results of the present study revealed that compared with those in the control group, PGP expression was reduced, and OATP2 expression was increased (p<0.001) in the TZ group. The real-time PCR results were validated by IHC, which revealed moderate to mild PGP staining and moderate to severe OATP2 staining in the TZ-treated rats. Additionally, GSH levels were significantly decreased and lipid peroxidation was increased in TZ treated rats as compared to untreated control. Furthermore, TZ tends to accumulate more (p<0.01) in brain tissues than blood in treated rats. These findings suggest that TZ may gain access to the BBB via potential interaction with OATP2, accumulate and induce oxidative stress, which may further contribute a new piece of evidence to the toxicity profile of TZ to reiterate the strict need to monitor the indiscriminate use of TZ in agricultural fields. Short running title: Neurotoxic effects of Triazophos