Sodium selenate

Post‐traumatic epilepsy (PTE) is a life‐long complication of traumatic brain injury (TBI). The development of PTE is associated with neurological morbidity and increases the risk of mortality. An aim of EpiBioS4Rx (Epilepsy Bioinformatics Study for Antiepileptogenic Therapy) was to test potential therapies to prevent the development of PTE in the lateral fluid percussion injury (LFPI) rat model of TBI, in which rats were subjected to injury at the left parietal cortex. Sodium selenate has been reported to be antiepileptogenic post‐TBI in rodent models by activating protein phosphatase 2A and reducing phosphorylated tau (p‐tau) protein. We aimed to characterize the pharmacokinetics (PK) and brain uptake of sodium selenate using naïve control and LFPI rats. Rats received either a single bolus dose or a single bolus dose followed by a 7‐day subcutaneous minipump infusion of sodium selenate. Sodium selenate and selenium concentrations in plasma and brain were analyzed and used for PK estimation and brain exposure assessment. Selenium concentrations rapidly increased after sodium selenate administration, demonstrating biotransformation from sodium selenate to selenium. Sodium selenate and selenium PK parameters were estimated using non‐compartmental analysis. Sodium selenate clearance (CL/F) and volume of distribution (Vd/F) varied by dose and route of administration, suggesting differences in bioavailability and nonlinear pharmacokinetics at the doses tested. Brain‐to‐plasma partition coefficients (AUCbrain/AUCplasma) for sodium selenate and selenium were found to be 0.7–1.3 and 0.1–0.3 following single‐dose injection, respectively, indicating active transport of sodium selenate across the blood–brain barrier (BBB).

Cadmium (Cd) and arsenic (As) have contrasting biogeochemical behaviors in paddy soil, which posed an obstacle for reducing their accumulation in rice (Oryza sativa L.) simultaneously. In this study, selenate exhibited a more effective ability than selenite on simultaneous alleviation of Cd and As accumulation in rice under Cd-As co-exposure, and the mechanisms need to be further investigated. The results showed that selenate significantly decreased the root Cd and As contents by 59%-83% and 43%-72% compared to Cd-As compound exposure, respectively. Correspondingly, it significantly down-regulated the expression of uptake-related genes OsNramp5 (87.1%) and OsLsi1 (95.5%) in rice roots. Decreases in Cd (64.5%) and As (16.2%) contents in shoots were also found after selenate addition. Moreover, selenate may promoted the reduction of As(V) to As(Ⅲ) and As(III) efflux to the external medium, resulting in decreased As accumulation and As(Ⅲ) proportion in rice shoots and roots. In addition, selenate could promote the binding of Cd (by 14%-24%) and As (by 9%-15%) in the cell wall, and significantly reduced the oxidative stress by elevating levels of antioxidant enzymes (by 10%-105%) and thiol compounds (by 6%-210%). Additionally, selenate significantly down-regulated the expression of OsNramp1 (49.3%) and OsLsi2 (82.1%) associated with Cd and As transport in rice. These findings suggest selenate has the potential to be an effective material for the simultaneous reduction of Cd and As accumulation in rice under Cd-As co-contamination.