Evaluation of Vanillin As a Probe Drug for Aldehyde Oxidase and Phenotyping for Its Activity in a Western Indian Cohort

Overview

Journal Indian J Pharmacol

Specialty Pharmacology

Date 2021 Jun 25

PMID 34169906

Citations 1

Authors

Sandhya Subash

Nithya J Gogtay

Krishna R Iyer

Prajakta Gandhe

Ritu Budania

Urmila M Thatte

Affiliations

Soon will be listed here.

Abstract

Background: Aldehyde oxidase (AO), a molybdoflavoenzyme, is emerging as a key player in drug discovery and metabolism. Despite having several known substrates, there are no validated probes reported for studying the activity of AO in vivo. Vanillin (4-hydroxy 3-methoxy benzaldehyde) is an excellent substrate of AO, in vitro. In the present study, vanillin has been validated as an in vivo probe for AO. Subsequently, a phenotyping study was carried out using vanillin in a subset of Indian population with 100 human volunteers.

Methods: For the purposes of in vitro probe validation, initially the metabolism of vanillin was characterized in partially purified guinea pig AO fraction. Further, vanillin was incubated with partially purified xanthine oxidase fraction and AO fractions, and liver microsomes obtained from different species (in presence and absence of specific inhibitors). For the phenotyping study, an oral dose of 500 mg of vanillin was administered to the participants in the study and cumulative urine samples were obtained up to 8 h after giving the dose. The samples were analyzed by high-performance liquid chromatography and metabolic ratios were calculated as peak area ratio of vanillic acid/vanillin.

Results: (a) The results of the in vitro validation studies clearly indicated that vanillin is preferentially metabolized by AO. (b) Normal distribution tests and probit analysis revealed that AO activity was not normally distributed and that 73.72% of the participants were fast metabolizers, 24.28% intermediate metabolizers, and 2% were slow metabolizers.

Conclusions: Data of the phenotyping study suggest the existence of AO polymorphism, in a Western Indian cohort.

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