Studies on Parkinson’s-Disease-Linked Genes, Brain Urea Levels and Histopathology in Rotenone Induced Parkinson’s Disease Rat Model

Parkinson’s disease (PD) is a debilitating neurological disorder that affects the aged population globally. This study aimed to explore how oral- and intraperitoneal-rotenone-induced PD alters brain urea levels, histopathology, and key Parkinsonism-related genes in the striatum. Hematoxylin and eosin staining was performed for histopathology assessment and real-time polymerase chain reaction was performed for gene expression. Rotenone 3 mg/kg body weight (Rot-3-ip) for 21 days and rotenone 50 mg/kg body weight (Rot-50-po) for 28 days significantly (p < 0.05) altered alpha-synuclein and tyrosine hydroxylase protein expression and Snca, Becn1 and Prkaa1 gene expression in the striatum. Lewy bodies were visible in both Rot-3-ip and Rot-50-po rat brains. There were contrasting features in brain and liver histopathology between the oral and intraperitoneal rotenone treatment groups. However, there was no significant (p < 0.05) difference in the brain urea levels between intraperitoneal and oral rotenone treatment groups. The propagation of PD through oral and intraperitoneal rotenone can have different impacts on the pathological sequence of events based on the molecular approach.

Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard

DRDE-07,a newly synthesized amifostine analog currently under clinical investigation in a phase I trial,is a potent antidote against sulfur mustard toxicity.The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg.The physicochemical properties of DRDE-07,including solubility,pK a,Log P,plasma protein binding and plasma/blood partitioning,were determined to support the pharmacokinetic characterization.DRDE-07 concentration was determined by an HPLC-UV method.The profile of plasma concentration versus time was analyzed using a non-compartmental model.Plasma protein binding was assessed using ultrafiltration.DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels(C max)observed in less than 15 min.There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing.The plasma protein binding of DRDE-07 was found to be less than 25%at all concentrations studied.Plasma clearance of DRDE-07 is expected to be?1.5 fold higher than the blood clearance of DRDE-07.The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.