Analysis of in silico and in vivo pharmacokinetic and toxicological parameters of dillapiole n-butyl ether.

Abstract

The larvicidal effect of dillapiole and its semi-synthetic derivatives on Aedes aegypti (Ae. Aegypti), the main transmitter of arboviruses such as dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV), is well - established. Among dillapiole derivatives, the n-butyl ether dillapiole stands out attributed to significant larvicidal potential against Ae. aegypti. However, studies are needed to assess the adverse risk following exposure to this chemical on non-target organisms. The aim of this study was to examine the risk of toxic consequences attributed to exposure to dillapiole n-butyl ether (DBE) by determining pharmacokinetic, biochemical and histopathological parameters. Dillapiole n-butyl ether was tested utilizing male Balb/C mice at concentrations of 10, 20 or 40 mg/kg. Subsequently, peripheral blood was obtained for biochemical analyses, kidney and livers for histopathological examination. DBE decreased serum creatinine levels et 10 or 40 mg/kg. Urea levels were reduced at 10 mg/kg but elevated at 20 mg/kg. Serum gamma-GT was significantly lowered at 40 mg/kg. Alkaline phosphatase activity was significantly decreased at 20 and 40 mg/kg/. In contrast, alanine aminotransferase activity was significantly elevated. At concentrations of 10 and 20 mg/kg DBE, dose-dependent elevation in number of binucleated hepatocytes, steatosis (micro- and macrovacuolar) and necrotic foci were observed. In kidney, progressive impairment of glomerular and tubular structure was detected accompanied by inflammation, degeneration, and cellular necrosis more pronounced at higher doses, resulting in significant loss of renal parenchyma at 40 mg/kg. Data demonstrate that DBE initiated dose-dependent hepatic and renal structural changes.