The Effect of Protein Restriction in the In Vitro Metabolism of Albendazole in Rats
Katia Roberta A. Belaz,
Josiane de O. Cardoso,
Carlos Alberto da Silva,
Regina V. Oliveira.
This work presents an in vitro investigation of the effect of protein restriction on the
metabolism of albendazole (ABZ). This study was conducted using liver microsomal fractions
obtained from Wistar rats. For the quantitative analysis, a multidimensional High Performance Liquid
Chromatography (2D HPLC) method was fully validated for the determination of the ABZ
metabolites: albendazole sulfoxide, albendazole sulfone and albendazole 2-aminesulfone.
The target compounds were directly extracted using a C8-RAM-BSA column (5.0 x 0.46 cm i.d.) and
analyzed on a chromatographic chiral column containing amylose tris(3,5-dimethylphenylcarbamate) (150 x 4.6 mm i.d.).
The in vitro biotransformation results showed that the protein restriction influenced the oxidative metabolism of ABZ. The
production of R-(+)-ABZ-SO (1309 nmol/L) and S-(-)-ABZ-SO (1456 nmol/L) was higher in the control animals than in the
animals fed with a diet containing 6% protein, which produced 778.7 nmol/L and 709.5 nmol/L for R-(+) and S-(-)-ABZ-SO
enantiomers, respectively. These results were statistically inspected by Student´s t test and the results showed a significant
difference between the two means (p < 0.05). Moreover, the production of ABZ-SO enantiomers was enantioselective
where the S-(-)-ABZ-SO was formed in greater amounts than the R-(+)-ABZ-SO in control animals (p = 0.0231).
However, the enantioselectivity was not observed when the in vitro biotransformation of ABZ was conducted using the
microsomal fractions obtained from protein restriction animals (p > 0.05). Furthermore, animal nutritional condition could
affect the pattern of ABZ sulphoxidation indicating that the protein nutrition affect primarily the formation of R-(+)-ABZSO
and S-(-)-ABZ-SO enantiomers.
Keywords: Albendazole metabolites, enantioselective metabolism, in vitro metabolism, multidimensional liquid
chromatography, protein restriction, rat liver microsomes.
Rights & PermissionsPrintExport